Cardiology

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.

Vigorous physical activity for 20 minutes a day was enough to maximize cardiorespiratory benefits in adolescents, based on data from more than 300 individuals.

Current recommendations for physical activity in children and adolescents from the World Health Organization call for moderate to vigorous physical activity (MVPA) for an average of 60 minutes a day for physical and mental health; however, guidance on how much physical activity teens need to maximize cardiorespiratory fitness (CRF) has not been determined, Samuel Joseph Burden, BMedSci, of John Radcliffe Hospital Oxford (England), and colleagues wrote.

“Although data in young people are limited, adult studies have shown that regular, brief vigorous physical activity is highly effective at improving health markers, including CRF, which is also an important marker of health in youth,” the researchers wrote.

In a study published in Pediatrics, the researchers examined the associations between physical activity intensity and maximal CRF. The study population included 339 adolescents aged 13-14 years who were evaluated during the 2018-2019 and 2019-2020 school years. Participants wore wrist accelerometers to measure the intensity of physical activity and participated in 20-meter shuttle runs to demonstrate CRF. The researchers used partial multivariable linear regression to assess variables at different intensities including moderate physical activity (MPA), light physical activity (LPA), and sedentary time, as well as vigorous physical activity (VPA).

The wrist monitors measured the intensities of physical activity based on the bandpass-filtered followed by Euclidean norm metric (BFEN), a validated metric. “Previously validated thresholds for BFEN were used to determine the average duration of daily physical activity at each intensity: 0.1 g for LPA, 0.314 g for MPA, and 0.998 g for VPA,” the researchers wrote. Physical activity below the threshold for LPA was categorized as sedentary time.

Participants wore the accelerometers for 1 week; value recording included at least 3 weekdays and 1 weekend day, and each valid day required more than 6 hours of awake time.

Overall, VPA for up to 20 minutes was significantly associated with improved CRF. However, the benefits on CRF plateaued after that time, and longer duration of VPA was not associated with significantly greater improvements in CRF. Neither MPA nor LPA were associated with any improvements in CRF.

Participants who engaged in an average of 14 minutes (range, 12-17 minutes) of VPA per day met the median CRF.

The researchers also conducted independent t tests to assess differences in VPA at different CRF thresholds.

Those in the highest quartile of VPA had CRF z scores 1.03 higher, compared with those in the lower quartiles.

Given that current PA guidelines involve a combination of moderate and vigorous PA that could be met by MPA with no VPA, the current findings have public health implications for improving CRF in adolescents, the researchers wrote.

Even with MPA as an option, most adolescents fail to meet the recommendations of at least 60 minutes of MVPA, they said. “One possible reason is that this duration is quite long, requiring a daily time commitment that some may find difficult to maintain. A shorter target of 20 minutes might be easier to schedule daily and a focus on VPA would simplify messages about the intensity of activity that is likely to improve CRF.”

The study findings were limited by several factors including the use of data from only two schools in the United Kingdom, which may limit generalizability, and future research would ideally include a more direct assessment of VO₂ max, the researchers wrote. However, the results were strengthened by the large and diverse study population, including teens with a wide range of body mass index as well as CRF.

Future research is needed to test whether interventions based on a target of 20 minutes of VPA creates significant improvements in adolescent cardiometabolic health, the researchers concluded.
 

Any activity has value for sedentary teens

The current study suggests that counseling teens about physical activity may be less challenging for clinicians if optimal cardiorespiratory benefits can be reached with shorter bouts of activity, Michele LaBotz, MD, of Intermed Sports Medicine, South Portland, Maine, and Sarah Hoffman, DO, of Tufts University, Boston, wrote in an accompanying editorial.

The results have two key implications for pediatricians, the authors said. First, “optimal CRF can be achieved with much shorter periods of activity than previously recommended.” Second, “current ‘moderate to vigorous’ PA recommendations may not be sufficient to improve CRF in adolescents, if achieved through moderate activity only.”

However, the editorialists emphasized that, although shorter periods of higher-intensity exercise reduce the time burden for teens and families, specific education is needed to explain the extra effort involved in exercising vigorously enough for cardiorespiratory benefits.

Patients can be counseled that activity is vigorous when they start to sweat, their face gets red, and they feel short of breath and unable to talk during activity,” they explained. These sensations may be new and uncomfortable for children and teens who have been quite sedentary or used to low-intensity activity. Dr. LaBotz and Dr. Hoffman advised pediatricians to counsel patients to build intensity gradually, with “exercise snacks,” that involve several minutes of activity that become more challenging over time.

“Exercise snacks can include anything that elevates the heart rate for a minute or more, such as running up and down the stairs a few times; chasing the dog around the backyard; or just putting on some music and dancing hard,” the editorialists wrote.

“Some exercise is better than none, and extrapolating from adult data, the biggest benefit likely occurs when we can help our most sedentary and least fit patients become a bit more active, even if it falls short of currently recommended levels,” they concluded.

The study was supported by grants to various researchers from the British Heart Foundation, the Elizabeth Casson Trust, the U.K. National Institute of Health Research, the Professor Nigel Groome Studentship scheme (Oxford Brookes University), and the U.K. Department of Health. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose.

Vigorous physical activity for 20 minutes a day was enough to maximize cardiorespiratory benefits in adolescents, based on data from more than 300 individuals.

Current recommendations for physical activity in children and adolescents from the World Health Organization call for moderate to vigorous physical activity (MVPA) for an average of 60 minutes a day for physical and mental health; however, guidance on how much physical activity teens need to maximize cardiorespiratory fitness (CRF) has not been determined, Samuel Joseph Burden, BMedSci, of John Radcliffe Hospital Oxford (England), and colleagues wrote.

“Although data in young people are limited, adult studies have shown that regular, brief vigorous physical activity is highly effective at improving health markers, including CRF, which is also an important marker of health in youth,” the researchers wrote.

In a study published in Pediatrics, the researchers examined the associations between physical activity intensity and maximal CRF. The study population included 339 adolescents aged 13-14 years who were evaluated during the 2018-2019 and 2019-2020 school years. Participants wore wrist accelerometers to measure the intensity of physical activity and participated in 20-meter shuttle runs to demonstrate CRF. The researchers used partial multivariable linear regression to assess variables at different intensities including moderate physical activity (MPA), light physical activity (LPA), and sedentary time, as well as vigorous physical activity (VPA).

The wrist monitors measured the intensities of physical activity based on the bandpass-filtered followed by Euclidean norm metric (BFEN), a validated metric. “Previously validated thresholds for BFEN were used to determine the average duration of daily physical activity at each intensity: 0.1 g for LPA, 0.314 g for MPA, and 0.998 g for VPA,” the researchers wrote. Physical activity below the threshold for LPA was categorized as sedentary time.

Participants wore the accelerometers for 1 week; value recording included at least 3 weekdays and 1 weekend day, and each valid day required more than 6 hours of awake time.

Overall, VPA for up to 20 minutes was significantly associated with improved CRF. However, the benefits on CRF plateaued after that time, and longer duration of VPA was not associated with significantly greater improvements in CRF. Neither MPA nor LPA were associated with any improvements in CRF.

Participants who engaged in an average of 14 minutes (range, 12-17 minutes) of VPA per day met the median CRF.

The researchers also conducted independent t tests to assess differences in VPA at different CRF thresholds.

Those in the highest quartile of VPA had CRF z scores 1.03 higher, compared with those in the lower quartiles.

Given that current PA guidelines involve a combination of moderate and vigorous PA that could be met by MPA with no VPA, the current findings have public health implications for improving CRF in adolescents, the researchers wrote.

Even with MPA as an option, most adolescents fail to meet the recommendations of at least 60 minutes of MVPA, they said. “One possible reason is that this duration is quite long, requiring a daily time commitment that some may find difficult to maintain. A shorter target of 20 minutes might be easier to schedule daily and a focus on VPA would simplify messages about the intensity of activity that is likely to improve CRF.”

The study findings were limited by several factors including the use of data from only two schools in the United Kingdom, which may limit generalizability, and future research would ideally include a more direct assessment of VO₂ max, the researchers wrote. However, the results were strengthened by the large and diverse study population, including teens with a wide range of body mass index as well as CRF.

Future research is needed to test whether interventions based on a target of 20 minutes of VPA creates significant improvements in adolescent cardiometabolic health, the researchers concluded.
 

Any activity has value for sedentary teens

The current study suggests that counseling teens about physical activity may be less challenging for clinicians if optimal cardiorespiratory benefits can be reached with shorter bouts of activity, Michele LaBotz, MD, of Intermed Sports Medicine, South Portland, Maine, and Sarah Hoffman, DO, of Tufts University, Boston, wrote in an accompanying editorial.

The results have two key implications for pediatricians, the authors said. First, “optimal CRF can be achieved with much shorter periods of activity than previously recommended.” Second, “current ‘moderate to vigorous’ PA recommendations may not be sufficient to improve CRF in adolescents, if achieved through moderate activity only.”

However, the editorialists emphasized that, although shorter periods of higher-intensity exercise reduce the time burden for teens and families, specific education is needed to explain the extra effort involved in exercising vigorously enough for cardiorespiratory benefits.

Patients can be counseled that activity is vigorous when they start to sweat, their face gets red, and they feel short of breath and unable to talk during activity,” they explained. These sensations may be new and uncomfortable for children and teens who have been quite sedentary or used to low-intensity activity. Dr. LaBotz and Dr. Hoffman advised pediatricians to counsel patients to build intensity gradually, with “exercise snacks,” that involve several minutes of activity that become more challenging over time.

“Exercise snacks can include anything that elevates the heart rate for a minute or more, such as running up and down the stairs a few times; chasing the dog around the backyard; or just putting on some music and dancing hard,” the editorialists wrote.

“Some exercise is better than none, and extrapolating from adult data, the biggest benefit likely occurs when we can help our most sedentary and least fit patients become a bit more active, even if it falls short of currently recommended levels,” they concluded.

The study was supported by grants to various researchers from the British Heart Foundation, the Elizabeth Casson Trust, the U.K. National Institute of Health Research, the Professor Nigel Groome Studentship scheme (Oxford Brookes University), and the U.K. Department of Health. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose.

Vigorous physical activity for 20 minutes a day was enough to maximize cardiorespiratory benefits in adolescents, based on data from more than 300 individuals.

Current recommendations for physical activity in children and adolescents from the World Health Organization call for moderate to vigorous physical activity (MVPA) for an average of 60 minutes a day for physical and mental health; however, guidance on how much physical activity teens need to maximize cardiorespiratory fitness (CRF) has not been determined, Samuel Joseph Burden, BMedSci, of John Radcliffe Hospital Oxford (England), and colleagues wrote.

“Although data in young people are limited, adult studies have shown that regular, brief vigorous physical activity is highly effective at improving health markers, including CRF, which is also an important marker of health in youth,” the researchers wrote.

In a study published in Pediatrics, the researchers examined the associations between physical activity intensity and maximal CRF. The study population included 339 adolescents aged 13-14 years who were evaluated during the 2018-2019 and 2019-2020 school years. Participants wore wrist accelerometers to measure the intensity of physical activity and participated in 20-meter shuttle runs to demonstrate CRF. The researchers used partial multivariable linear regression to assess variables at different intensities including moderate physical activity (MPA), light physical activity (LPA), and sedentary time, as well as vigorous physical activity (VPA).

The wrist monitors measured the intensities of physical activity based on the bandpass-filtered followed by Euclidean norm metric (BFEN), a validated metric. “Previously validated thresholds for BFEN were used to determine the average duration of daily physical activity at each intensity: 0.1 g for LPA, 0.314 g for MPA, and 0.998 g for VPA,” the researchers wrote. Physical activity below the threshold for LPA was categorized as sedentary time.

Participants wore the accelerometers for 1 week; value recording included at least 3 weekdays and 1 weekend day, and each valid day required more than 6 hours of awake time.

Overall, VPA for up to 20 minutes was significantly associated with improved CRF. However, the benefits on CRF plateaued after that time, and longer duration of VPA was not associated with significantly greater improvements in CRF. Neither MPA nor LPA were associated with any improvements in CRF.

Participants who engaged in an average of 14 minutes (range, 12-17 minutes) of VPA per day met the median CRF.

The researchers also conducted independent t tests to assess differences in VPA at different CRF thresholds.

Those in the highest quartile of VPA had CRF z scores 1.03 higher, compared with those in the lower quartiles.

Given that current PA guidelines involve a combination of moderate and vigorous PA that could be met by MPA with no VPA, the current findings have public health implications for improving CRF in adolescents, the researchers wrote.

Even with MPA as an option, most adolescents fail to meet the recommendations of at least 60 minutes of MVPA, they said. “One possible reason is that this duration is quite long, requiring a daily time commitment that some may find difficult to maintain. A shorter target of 20 minutes might be easier to schedule daily and a focus on VPA would simplify messages about the intensity of activity that is likely to improve CRF.”

The study findings were limited by several factors including the use of data from only two schools in the United Kingdom, which may limit generalizability, and future research would ideally include a more direct assessment of VO₂ max, the researchers wrote. However, the results were strengthened by the large and diverse study population, including teens with a wide range of body mass index as well as CRF.

Future research is needed to test whether interventions based on a target of 20 minutes of VPA creates significant improvements in adolescent cardiometabolic health, the researchers concluded.
 

Any activity has value for sedentary teens

The current study suggests that counseling teens about physical activity may be less challenging for clinicians if optimal cardiorespiratory benefits can be reached with shorter bouts of activity, Michele LaBotz, MD, of Intermed Sports Medicine, South Portland, Maine, and Sarah Hoffman, DO, of Tufts University, Boston, wrote in an accompanying editorial.

The results have two key implications for pediatricians, the authors said. First, “optimal CRF can be achieved with much shorter periods of activity than previously recommended.” Second, “current ‘moderate to vigorous’ PA recommendations may not be sufficient to improve CRF in adolescents, if achieved through moderate activity only.”

However, the editorialists emphasized that, although shorter periods of higher-intensity exercise reduce the time burden for teens and families, specific education is needed to explain the extra effort involved in exercising vigorously enough for cardiorespiratory benefits.

Patients can be counseled that activity is vigorous when they start to sweat, their face gets red, and they feel short of breath and unable to talk during activity,” they explained. These sensations may be new and uncomfortable for children and teens who have been quite sedentary or used to low-intensity activity. Dr. LaBotz and Dr. Hoffman advised pediatricians to counsel patients to build intensity gradually, with “exercise snacks,” that involve several minutes of activity that become more challenging over time.

“Exercise snacks can include anything that elevates the heart rate for a minute or more, such as running up and down the stairs a few times; chasing the dog around the backyard; or just putting on some music and dancing hard,” the editorialists wrote.

“Some exercise is better than none, and extrapolating from adult data, the biggest benefit likely occurs when we can help our most sedentary and least fit patients become a bit more active, even if it falls short of currently recommended levels,” they concluded.

The study was supported by grants to various researchers from the British Heart Foundation, the Elizabeth Casson Trust, the U.K. National Institute of Health Research, the Professor Nigel Groome Studentship scheme (Oxford Brookes University), and the U.K. Department of Health. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose.

NEW ORLEANS – The case continues to grow for prioritizing a sodium-glucose transporter 2 (SGLT2) inhibitor in patients with type 2 diabetes, as real-world evidence of benefit and safety accumulates on top of the data from randomized trials that first established this class as a management pillar.

Another important effect of these agents gaining increasing currency, on top of their well-established benefits in patients with type 2 diabetes for preventing acute heart failure exacerbations and slowing progression of diabetic kidney disease, is that they cut the incidence of new-onset atrial fibrillation (AFib). That effect was confirmed in an analysis of data from about 300,000 U.S. patients included in recent Medicare records, Elisabetta Patorno, MD, reported at the annual scientific sessions of the American Diabetes Association.

Mitchel L. Zoler/MDedge News

But despite documentation like this, real-world evidence also continues to show limited uptake of SGLT2 inhibitors in U.S. patients with type 2 diabetes. Records from more than 1.3 million patients with type 2 diabetes managed in the Veterans Affairs Healthcare System during 2019 or 2022 documented that just 10% of these patients received an agent from this class, even though all were eligible to receive it, according to findings in a separate report at the meeting.

The AFib analysis analyzed two sets of propensity score–matched Medicare patients during 2013-2018 aged 65 years or older with type 2 diabetes and no history of AFib. One analysis focused on 80,475 matched patients who started on treatment with either an SGLT2 inhibitor or a glucagonlike peptide–1 (GLP-1) receptor agonist, and a second on 74,868 matched patients who began either an SGTL2 inhibitor or a dipeptidyl peptidase–4 (DPP4) inhibitor. In both analyses, matching involved more than 130 variables. In both pair sets, patients at baseline averaged about 72 years old, nearly two-thirds were women, about 8%-9% had heart failure, 77%-80% were on metformin, and 20%-25% were using insulin.

The study’s primary endpoint was the incidence of hospitalization for AFib, which occurred a significant 18% less often in the patients who started on an SGLT2, compared with those who started a DPP4 inhibitor during median follow-up of 6.7 months, and a significant 10% less often, compared with those starting a GLP-1 receptor agonist during a median follow-up of 6.0 months, Elisabetta Patorno, MD, DrPH, reported at the meeting. This worked out to 3.7 fewer hospitalizations for AFib per 1,000 patient-years of follow-up among the people who received an SGLT2 inhibitor, compared with a DPP4 inhibitor, and a decrease of 1.8 hospitalizations/1,000 patient-years when compared against patients in a GLP-1 receptor agonist.

Two secondary outcomes showed significantly fewer episodes of newly diagnosed AFib, and significantly fewer patients initiating AFib treatment among those who received an SGLT2 inhibitor relative to the comparator groups. In addition, these associations were consistent across subgroup analyses that divided patients by their age, sex, history of heart failure, and history of atherosclerotic cardiovascular disease.
 

AFib effects add to benefits

The findings “suggest that initiation of an SGLT2 inhibitor may be beneficial in older adults with type 2 diabetes who are at risk for AFib,” said Dr. Patorno, a researcher in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston. “These new findings on AFib may be helpful when weighing the potential risks and benefits of various glucose-lowering drugs in older patients with type 2 diabetes.”

This new evidence follows several prior reports from other research groups of data supporting an AFib benefit from SGLT2 inhibitors. The earlier reports include a post hoc analysis of more than 17,000 patients enrolled in the DECLARE-TIMI 58 cardiovascular outcome trial of dapagliflozin (Farxiga), which showed a 19% relative decrease in the rate of incident AFib or atrial flutter events during a median 4.2 year follow-up.

Other prior reports that found a reduced incidence of AFib events linked with SGLT2 inhibitor treatment include a 2020 meta-analysis based on data from more than 38,000 patients with type 2 diabetes enrolled in any of 16 randomized, controlled trials, which found a 24% relative risk reduction. And an as-yet unpublished report from researchers at the University of Rochester (N.Y.) and their associates presented in November 2021 at the annual scientific sessions of the American Heart Association that documented a significant 24% relative risk reduction in incident AFib events linked to SGLT2 inhibitor treatment in a prospective study of 13,890 patients at several hospitals in Israel or the United States.
 

Evidence ‘convincing’ in totality

The accumulated evidence for a reduced incidence of AFib when patients were on treatment with an SGLT2 inhibitor are “convincing because it’s real world data that complements what we know from clinical trials,” commented Silvio E. Inzucchi, MD, professor of medicine at Yale University and director of the Yale Medicine Diabetes Center in New Haven, Conn., who was not involved with the study.

“If these drugs reduce heart failure, they may also reduce AFib. Heart failure patients easily slip into AFib,” he noted in an interview, but added that “I don’t think this explains all cases” of the reduced AFib incidence.

Dr. Patorno offered a few other possible mechanisms for the observed effect. The class may work by reducing blood pressure, weight, inflammation, and oxidative stress, mitochondrial dysfunction, atrial remodeling, and AFib susceptibility. These agents are also known to cause natriuresis and diuresis, which could reduce atrial dilation, a mechanism that again relates the AFib effect to the better documented reduction in acute heart failure exacerbations.

“With the diuretic effect, we’d expect less overload at the atrium and less dilation, and the same mechanism would reduce heart failure,” she said in an interview.

“If you reduce preload and afterload you may reduce stress on the ventricle and reduce atrial stretch, and that might have a significant effect on atrial arrhythmia,” agreed Dr. Inzucchi.
 

EMPRISE produces more real-world evidence

A pair of additional reports at the meeting that Dr. Patorno coauthored provided real-world evidence supporting the dramatic heart failure benefit of the SGLT2 inhibitor empagliflozin (Jardiance) in U.S. patients with type 2 diabetes, compared with alternative drug classes. The EMPRISE study used data from the Medicare, Optum Clinformatics, and MarketScan databases during the period from August 2014, when empagliflozin became available, to September 2019. The study used more than 140 variables to match patients treated with either empagliflozin or a comparator agent.

The results showed that, in an analysis of more than 130,000 matched pairs, treatment with empagliflozin was linked to a significant 30% reduction in the incidence of hospitalization for heart failure, compared with patients treated with a GLP-1 receptor agonist. Analysis of more than 116,000 matched pairs of patients showed that treatment with empagliflozin linked with a significant 29%-50% reduced rate of hospitalization for heart failure, compared with matched patients treated with a DPP4 inhibitor.

These findings “add to the pool of information” on the efficacy of agents from the SGLT2 inhibitor class, Dr. Patorno said in an interview. “We wanted to look at the full range of patients with type 2 diabetes who we see in practice,” rather than the more selected group of patients enrolled in randomized trials.

SGLT2 inhibitor use lags even when cost isn’t an issue

Despite all the accumulated evidence for efficacy and safety of the class, usage remains low, Julio A. Lamprea-Montealegre, MD, PhD, a cardiologist at the University of California, San Francisco, reported in a separate talk at the meeting. The study he presented examined records for 1,319,500 adults with type 2 diabetes managed in the VA Healthcare System during 2019 and 2020. Despite being in a system that “removes the influence of cost,” just 10% of these patients received treatment with an SGLT2 inhibitor, and 7% received treatment with a GLP-1 receptor agonist.

Notably, his analysis further showed that treatment with an SGLT2 inhibitor was especially depressed among patients with an estimated glomerular filtration rate (eGFR) of 30-44 mL/min per 1.73m². In this subgroup, usage of a drug from this class was at two-thirds of the rate, compared with patients with an eGFR of at least 90 mL/min per 1.73m2. His findings also documented lower rates of use in patients with higher risk for atherosclerotic cardiovascular disease. Dr. Lamprea-Montealegre called this a “treatment paradox,” in which patients likely to get the most benefit from an SGLT2 inhibitor were also less likely to actually receive it.

While his findings from the VA System suggest that drug cost is not the only factor driving underuse, the high price set for the SGLT2 inhibitor drugs that all currently remain on U.S. patents is widely considered an important factor.

“There is a big problem of affordability,” said Dr. Patorno.

“SGLT2 inhibitors should probably be first-line therapy” for many patients with type 2 diabetes, said Dr. Inzucchi. “The only thing holding it back is cost,” a situation that he hopes will dramatically shift once agents from this class become generic and have substantially lower price tags.

The EMPRISE study received funding from Boehringer Ingelheim, the company that markets empagliflozin (Jardiance). Dr. Patorno had no relevant commercial disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk. Dr. Lamprea-Montealegre had received research funding from Bayer.

NEW ORLEANS – The case continues to grow for prioritizing a sodium-glucose transporter 2 (SGLT2) inhibitor in patients with type 2 diabetes, as real-world evidence of benefit and safety accumulates on top of the data from randomized trials that first established this class as a management pillar.

Another important effect of these agents gaining increasing currency, on top of their well-established benefits in patients with type 2 diabetes for preventing acute heart failure exacerbations and slowing progression of diabetic kidney disease, is that they cut the incidence of new-onset atrial fibrillation (AFib). That effect was confirmed in an analysis of data from about 300,000 U.S. patients included in recent Medicare records, Elisabetta Patorno, MD, reported at the annual scientific sessions of the American Diabetes Association.

Mitchel L. Zoler/MDedge News

But despite documentation like this, real-world evidence also continues to show limited uptake of SGLT2 inhibitors in U.S. patients with type 2 diabetes. Records from more than 1.3 million patients with type 2 diabetes managed in the Veterans Affairs Healthcare System during 2019 or 2022 documented that just 10% of these patients received an agent from this class, even though all were eligible to receive it, according to findings in a separate report at the meeting.

The AFib analysis analyzed two sets of propensity score–matched Medicare patients during 2013-2018 aged 65 years or older with type 2 diabetes and no history of AFib. One analysis focused on 80,475 matched patients who started on treatment with either an SGLT2 inhibitor or a glucagonlike peptide–1 (GLP-1) receptor agonist, and a second on 74,868 matched patients who began either an SGTL2 inhibitor or a dipeptidyl peptidase–4 (DPP4) inhibitor. In both analyses, matching involved more than 130 variables. In both pair sets, patients at baseline averaged about 72 years old, nearly two-thirds were women, about 8%-9% had heart failure, 77%-80% were on metformin, and 20%-25% were using insulin.

The study’s primary endpoint was the incidence of hospitalization for AFib, which occurred a significant 18% less often in the patients who started on an SGLT2, compared with those who started a DPP4 inhibitor during median follow-up of 6.7 months, and a significant 10% less often, compared with those starting a GLP-1 receptor agonist during a median follow-up of 6.0 months, Elisabetta Patorno, MD, DrPH, reported at the meeting. This worked out to 3.7 fewer hospitalizations for AFib per 1,000 patient-years of follow-up among the people who received an SGLT2 inhibitor, compared with a DPP4 inhibitor, and a decrease of 1.8 hospitalizations/1,000 patient-years when compared against patients in a GLP-1 receptor agonist.

Two secondary outcomes showed significantly fewer episodes of newly diagnosed AFib, and significantly fewer patients initiating AFib treatment among those who received an SGLT2 inhibitor relative to the comparator groups. In addition, these associations were consistent across subgroup analyses that divided patients by their age, sex, history of heart failure, and history of atherosclerotic cardiovascular disease.
 

AFib effects add to benefits

The findings “suggest that initiation of an SGLT2 inhibitor may be beneficial in older adults with type 2 diabetes who are at risk for AFib,” said Dr. Patorno, a researcher in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston. “These new findings on AFib may be helpful when weighing the potential risks and benefits of various glucose-lowering drugs in older patients with type 2 diabetes.”

This new evidence follows several prior reports from other research groups of data supporting an AFib benefit from SGLT2 inhibitors. The earlier reports include a post hoc analysis of more than 17,000 patients enrolled in the DECLARE-TIMI 58 cardiovascular outcome trial of dapagliflozin (Farxiga), which showed a 19% relative decrease in the rate of incident AFib or atrial flutter events during a median 4.2 year follow-up.

Other prior reports that found a reduced incidence of AFib events linked with SGLT2 inhibitor treatment include a 2020 meta-analysis based on data from more than 38,000 patients with type 2 diabetes enrolled in any of 16 randomized, controlled trials, which found a 24% relative risk reduction. And an as-yet unpublished report from researchers at the University of Rochester (N.Y.) and their associates presented in November 2021 at the annual scientific sessions of the American Heart Association that documented a significant 24% relative risk reduction in incident AFib events linked to SGLT2 inhibitor treatment in a prospective study of 13,890 patients at several hospitals in Israel or the United States.
 

Evidence ‘convincing’ in totality

The accumulated evidence for a reduced incidence of AFib when patients were on treatment with an SGLT2 inhibitor are “convincing because it’s real world data that complements what we know from clinical trials,” commented Silvio E. Inzucchi, MD, professor of medicine at Yale University and director of the Yale Medicine Diabetes Center in New Haven, Conn., who was not involved with the study.

“If these drugs reduce heart failure, they may also reduce AFib. Heart failure patients easily slip into AFib,” he noted in an interview, but added that “I don’t think this explains all cases” of the reduced AFib incidence.

Dr. Patorno offered a few other possible mechanisms for the observed effect. The class may work by reducing blood pressure, weight, inflammation, and oxidative stress, mitochondrial dysfunction, atrial remodeling, and AFib susceptibility. These agents are also known to cause natriuresis and diuresis, which could reduce atrial dilation, a mechanism that again relates the AFib effect to the better documented reduction in acute heart failure exacerbations.

“With the diuretic effect, we’d expect less overload at the atrium and less dilation, and the same mechanism would reduce heart failure,” she said in an interview.

“If you reduce preload and afterload you may reduce stress on the ventricle and reduce atrial stretch, and that might have a significant effect on atrial arrhythmia,” agreed Dr. Inzucchi.
 

EMPRISE produces more real-world evidence

A pair of additional reports at the meeting that Dr. Patorno coauthored provided real-world evidence supporting the dramatic heart failure benefit of the SGLT2 inhibitor empagliflozin (Jardiance) in U.S. patients with type 2 diabetes, compared with alternative drug classes. The EMPRISE study used data from the Medicare, Optum Clinformatics, and MarketScan databases during the period from August 2014, when empagliflozin became available, to September 2019. The study used more than 140 variables to match patients treated with either empagliflozin or a comparator agent.

The results showed that, in an analysis of more than 130,000 matched pairs, treatment with empagliflozin was linked to a significant 30% reduction in the incidence of hospitalization for heart failure, compared with patients treated with a GLP-1 receptor agonist. Analysis of more than 116,000 matched pairs of patients showed that treatment with empagliflozin linked with a significant 29%-50% reduced rate of hospitalization for heart failure, compared with matched patients treated with a DPP4 inhibitor.

These findings “add to the pool of information” on the efficacy of agents from the SGLT2 inhibitor class, Dr. Patorno said in an interview. “We wanted to look at the full range of patients with type 2 diabetes who we see in practice,” rather than the more selected group of patients enrolled in randomized trials.

SGLT2 inhibitor use lags even when cost isn’t an issue

Despite all the accumulated evidence for efficacy and safety of the class, usage remains low, Julio A. Lamprea-Montealegre, MD, PhD, a cardiologist at the University of California, San Francisco, reported in a separate talk at the meeting. The study he presented examined records for 1,319,500 adults with type 2 diabetes managed in the VA Healthcare System during 2019 and 2020. Despite being in a system that “removes the influence of cost,” just 10% of these patients received treatment with an SGLT2 inhibitor, and 7% received treatment with a GLP-1 receptor agonist.

Notably, his analysis further showed that treatment with an SGLT2 inhibitor was especially depressed among patients with an estimated glomerular filtration rate (eGFR) of 30-44 mL/min per 1.73m². In this subgroup, usage of a drug from this class was at two-thirds of the rate, compared with patients with an eGFR of at least 90 mL/min per 1.73m2. His findings also documented lower rates of use in patients with higher risk for atherosclerotic cardiovascular disease. Dr. Lamprea-Montealegre called this a “treatment paradox,” in which patients likely to get the most benefit from an SGLT2 inhibitor were also less likely to actually receive it.

While his findings from the VA System suggest that drug cost is not the only factor driving underuse, the high price set for the SGLT2 inhibitor drugs that all currently remain on U.S. patents is widely considered an important factor.

“There is a big problem of affordability,” said Dr. Patorno.

“SGLT2 inhibitors should probably be first-line therapy” for many patients with type 2 diabetes, said Dr. Inzucchi. “The only thing holding it back is cost,” a situation that he hopes will dramatically shift once agents from this class become generic and have substantially lower price tags.

The EMPRISE study received funding from Boehringer Ingelheim, the company that markets empagliflozin (Jardiance). Dr. Patorno had no relevant commercial disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk. Dr. Lamprea-Montealegre had received research funding from Bayer.

NEW ORLEANS – The case continues to grow for prioritizing a sodium-glucose transporter 2 (SGLT2) inhibitor in patients with type 2 diabetes, as real-world evidence of benefit and safety accumulates on top of the data from randomized trials that first established this class as a management pillar.

Another important effect of these agents gaining increasing currency, on top of their well-established benefits in patients with type 2 diabetes for preventing acute heart failure exacerbations and slowing progression of diabetic kidney disease, is that they cut the incidence of new-onset atrial fibrillation (AFib). That effect was confirmed in an analysis of data from about 300,000 U.S. patients included in recent Medicare records, Elisabetta Patorno, MD, reported at the annual scientific sessions of the American Diabetes Association.

Mitchel L. Zoler/MDedge News

But despite documentation like this, real-world evidence also continues to show limited uptake of SGLT2 inhibitors in U.S. patients with type 2 diabetes. Records from more than 1.3 million patients with type 2 diabetes managed in the Veterans Affairs Healthcare System during 2019 or 2022 documented that just 10% of these patients received an agent from this class, even though all were eligible to receive it, according to findings in a separate report at the meeting.

The AFib analysis analyzed two sets of propensity score–matched Medicare patients during 2013-2018 aged 65 years or older with type 2 diabetes and no history of AFib. One analysis focused on 80,475 matched patients who started on treatment with either an SGLT2 inhibitor or a glucagonlike peptide–1 (GLP-1) receptor agonist, and a second on 74,868 matched patients who began either an SGTL2 inhibitor or a dipeptidyl peptidase–4 (DPP4) inhibitor. In both analyses, matching involved more than 130 variables. In both pair sets, patients at baseline averaged about 72 years old, nearly two-thirds were women, about 8%-9% had heart failure, 77%-80% were on metformin, and 20%-25% were using insulin.

The study’s primary endpoint was the incidence of hospitalization for AFib, which occurred a significant 18% less often in the patients who started on an SGLT2, compared with those who started a DPP4 inhibitor during median follow-up of 6.7 months, and a significant 10% less often, compared with those starting a GLP-1 receptor agonist during a median follow-up of 6.0 months, Elisabetta Patorno, MD, DrPH, reported at the meeting. This worked out to 3.7 fewer hospitalizations for AFib per 1,000 patient-years of follow-up among the people who received an SGLT2 inhibitor, compared with a DPP4 inhibitor, and a decrease of 1.8 hospitalizations/1,000 patient-years when compared against patients in a GLP-1 receptor agonist.

Two secondary outcomes showed significantly fewer episodes of newly diagnosed AFib, and significantly fewer patients initiating AFib treatment among those who received an SGLT2 inhibitor relative to the comparator groups. In addition, these associations were consistent across subgroup analyses that divided patients by their age, sex, history of heart failure, and history of atherosclerotic cardiovascular disease.
 

AFib effects add to benefits

The findings “suggest that initiation of an SGLT2 inhibitor may be beneficial in older adults with type 2 diabetes who are at risk for AFib,” said Dr. Patorno, a researcher in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston. “These new findings on AFib may be helpful when weighing the potential risks and benefits of various glucose-lowering drugs in older patients with type 2 diabetes.”

This new evidence follows several prior reports from other research groups of data supporting an AFib benefit from SGLT2 inhibitors. The earlier reports include a post hoc analysis of more than 17,000 patients enrolled in the DECLARE-TIMI 58 cardiovascular outcome trial of dapagliflozin (Farxiga), which showed a 19% relative decrease in the rate of incident AFib or atrial flutter events during a median 4.2 year follow-up.

Other prior reports that found a reduced incidence of AFib events linked with SGLT2 inhibitor treatment include a 2020 meta-analysis based on data from more than 38,000 patients with type 2 diabetes enrolled in any of 16 randomized, controlled trials, which found a 24% relative risk reduction. And an as-yet unpublished report from researchers at the University of Rochester (N.Y.) and their associates presented in November 2021 at the annual scientific sessions of the American Heart Association that documented a significant 24% relative risk reduction in incident AFib events linked to SGLT2 inhibitor treatment in a prospective study of 13,890 patients at several hospitals in Israel or the United States.
 

Evidence ‘convincing’ in totality

The accumulated evidence for a reduced incidence of AFib when patients were on treatment with an SGLT2 inhibitor are “convincing because it’s real world data that complements what we know from clinical trials,” commented Silvio E. Inzucchi, MD, professor of medicine at Yale University and director of the Yale Medicine Diabetes Center in New Haven, Conn., who was not involved with the study.

“If these drugs reduce heart failure, they may also reduce AFib. Heart failure patients easily slip into AFib,” he noted in an interview, but added that “I don’t think this explains all cases” of the reduced AFib incidence.

Dr. Patorno offered a few other possible mechanisms for the observed effect. The class may work by reducing blood pressure, weight, inflammation, and oxidative stress, mitochondrial dysfunction, atrial remodeling, and AFib susceptibility. These agents are also known to cause natriuresis and diuresis, which could reduce atrial dilation, a mechanism that again relates the AFib effect to the better documented reduction in acute heart failure exacerbations.

“With the diuretic effect, we’d expect less overload at the atrium and less dilation, and the same mechanism would reduce heart failure,” she said in an interview.

“If you reduce preload and afterload you may reduce stress on the ventricle and reduce atrial stretch, and that might have a significant effect on atrial arrhythmia,” agreed Dr. Inzucchi.
 

EMPRISE produces more real-world evidence

A pair of additional reports at the meeting that Dr. Patorno coauthored provided real-world evidence supporting the dramatic heart failure benefit of the SGLT2 inhibitor empagliflozin (Jardiance) in U.S. patients with type 2 diabetes, compared with alternative drug classes. The EMPRISE study used data from the Medicare, Optum Clinformatics, and MarketScan databases during the period from August 2014, when empagliflozin became available, to September 2019. The study used more than 140 variables to match patients treated with either empagliflozin or a comparator agent.

The results showed that, in an analysis of more than 130,000 matched pairs, treatment with empagliflozin was linked to a significant 30% reduction in the incidence of hospitalization for heart failure, compared with patients treated with a GLP-1 receptor agonist. Analysis of more than 116,000 matched pairs of patients showed that treatment with empagliflozin linked with a significant 29%-50% reduced rate of hospitalization for heart failure, compared with matched patients treated with a DPP4 inhibitor.

These findings “add to the pool of information” on the efficacy of agents from the SGLT2 inhibitor class, Dr. Patorno said in an interview. “We wanted to look at the full range of patients with type 2 diabetes who we see in practice,” rather than the more selected group of patients enrolled in randomized trials.

SGLT2 inhibitor use lags even when cost isn’t an issue

Despite all the accumulated evidence for efficacy and safety of the class, usage remains low, Julio A. Lamprea-Montealegre, MD, PhD, a cardiologist at the University of California, San Francisco, reported in a separate talk at the meeting. The study he presented examined records for 1,319,500 adults with type 2 diabetes managed in the VA Healthcare System during 2019 and 2020. Despite being in a system that “removes the influence of cost,” just 10% of these patients received treatment with an SGLT2 inhibitor, and 7% received treatment with a GLP-1 receptor agonist.

Notably, his analysis further showed that treatment with an SGLT2 inhibitor was especially depressed among patients with an estimated glomerular filtration rate (eGFR) of 30-44 mL/min per 1.73m². In this subgroup, usage of a drug from this class was at two-thirds of the rate, compared with patients with an eGFR of at least 90 mL/min per 1.73m2. His findings also documented lower rates of use in patients with higher risk for atherosclerotic cardiovascular disease. Dr. Lamprea-Montealegre called this a “treatment paradox,” in which patients likely to get the most benefit from an SGLT2 inhibitor were also less likely to actually receive it.

While his findings from the VA System suggest that drug cost is not the only factor driving underuse, the high price set for the SGLT2 inhibitor drugs that all currently remain on U.S. patents is widely considered an important factor.

“There is a big problem of affordability,” said Dr. Patorno.

“SGLT2 inhibitors should probably be first-line therapy” for many patients with type 2 diabetes, said Dr. Inzucchi. “The only thing holding it back is cost,” a situation that he hopes will dramatically shift once agents from this class become generic and have substantially lower price tags.

The EMPRISE study received funding from Boehringer Ingelheim, the company that markets empagliflozin (Jardiance). Dr. Patorno had no relevant commercial disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk. Dr. Lamprea-Montealegre had received research funding from Bayer.

Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.

In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.

The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.

But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.

“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”

The EMERGE study was published online  in JAMA Cardiology.

In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.

In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.

But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).

The EMERGE trial was conducted in this latter group without ST elevation.

For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.

The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).

There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.

Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.

However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.

Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.

“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.

In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.

“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.

Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.

“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.

In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.

The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.

But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.

“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”

The EMERGE study was published online  in JAMA Cardiology.

In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.

In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.

But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).

The EMERGE trial was conducted in this latter group without ST elevation.

For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.

The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).

There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.

Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.

However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.

Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.

“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.

In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.

“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.

Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.

“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.

In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.

The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.

But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.

“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”

The EMERGE study was published online  in JAMA Cardiology.

In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.

In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.

But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).

The EMERGE trial was conducted in this latter group without ST elevation.

For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.

The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).

There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.

Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.

However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.

Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.

“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.

In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.

“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.

Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.

“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Despite a new meta-analysis claiming to show that testosterone replacement therapy for men with hypogonadism does not increase the risk of cardiovascular outcomes such as myocardial infarction or stroke, experts say the jury is still out.

A more definitive answer for cardiovascular safety of testosterone therapy will come from the TRAVERSE dedicated cardiovascular outcome trial, sponsored by AbbVie, which will have up to 5 years of follow-up, with results expected later this year.

The current meta-analysis by Jemma Hudson of Aberdeen (Scotland) University and colleagues was published online in The Lancet Healthy Longevity. The work will also be presented June 13 at ENDO 2022, the Endocrine Society’s annual meeting in Atlanta, Georgia, by senior author Channa Y. Jayasena, MD, PhD.

In 2014, the U.S. Food and Drug Administration mandated a label on testosterone products warning of possible increased cardiovascular risks and to reserve the therapy for symptomatic hypogonadism only. In contrast, the European Medicines Agency concluded that when hypogonadism is properly diagnosed and managed, there is currently no clear, consistent evidence that testosterone therapy causes increased cardiovascular risk.

To address this uncertainty, Dr. Hudson and colleagues formed a global collaborative to obtain individual patient data on cardiovascular outcomes from randomized controlled trials of testosterone therapy for men with hypogonadism.

They pooled data from 35 trials published from 1992 to Aug. 27, 2018, including 17 trials (3,431 patients) for which the researchers obtained patient-level data. The individual trials were 3-12 months long, except for one 3-year trial.

During a mean follow-up of 9.5 months, there was no significant increase in cardiovascular outcomes in men randomized to testosterone therapy versus placebo (odds ratio, 1.07; P = .62), nor were there any significantly increased risks of death, stroke, or different types of cardiovascular outcome, although those numbers were small.  

This is “the most comprehensive study to date investigating the safety of testosterone treatment of hypogonadism,” according to the researchers. “The current results provide some reassurance about the short-term to medium-term safety of testosterone to treat male hypogonadism,” they conclude.

However, they also acknowledge that “long-term data are needed to fully evaluate the safety of testosterone.”

Erin D. Michos, MD, coauthor of an accompanying editorial, told this news organization, “This study doesn’t say to me that low testosterone necessarily needs to be treated. It’s still not indicated in people just for a low number [for blood testosterone] with less-severe symptoms. It really comes down to each individual person, how symptomatic they are, and their cardiovascular risk.”

‘Trial is not definitive’

Dr. Michos is not the only person to be skeptical. Together with Steven Nissen, MD, an investigator for the TRAVERSE trial, she agrees that this new evidence is not yet decisive, largely because the individual trials in the meta-analysis were short and not designed as cardiovascular outcome trials.

Dr. Nissen, a cardiologist at Cleveland Clinic, added that the individual trials were heterogeneous, with “very few real cardiovascular events,” so the meta-analysis “is not definitive,” he said in an interview.

While this meta-analysis “that pooled together a lot of smaller studies is reassuring that there’s no signal of harm, it’s really inconclusive because the follow-up was really short – a mean of only 9.5 months – and you really need a larger study with longer follow up to be more conclusive,” Dr. Michos noted.

“We should have more data soon” from TRAVERSE, said Dr. Michos, from the division of cardiology, Johns Hopkins University, Baltimore, who is not involved with that study.

Meanwhile, “I don’t think [this analysis] changes the current recommendations,” she said.

“We should continue to use caution as indicated by the FDA label and only use testosterone therapy selectively in people who have true symptoms of hypogonadism,” and be cautious about using it particularly in men at higher cardiovascular risk because of family history or known personal heart disease.

On the other hand, the meta-analysis did not show harm, she noted, “so we don’t necessarily need to pull patients off therapy if they are already taking it. But I wouldn’t right now just start new patients on it unless they had a strong indication.”

“Certainly, great caution is advised regarding the use of testosterone replacement therapy in people with established atherosclerosis due to the findings of plaque progression in the testosterone trials and the excess cardiovascular events observed in the TOM trial, write Dr. Michos and fellow editorialist Matthew J. Budoff, MD, of University of California, Los Angeles, in their editorial.
 

Earlier data inconclusive

Testosterone concentrations progressively decline in men with advancing age, at about 2% per year, Dr. Michos and Dr. Budoff write. In addition, men with obesity or with diabetes have low levels of testosterone, Dr. Michos noted.

Low testosterone blood levels have been associated with insulin resistance, inflammation, dyslipidemia, and atherosclerosis. Testosterone replacement therapy has been used to increase libido, improve erectile dysfunction, and boost energy levels, mood, and muscle strength.

But it is well known that testosterone increases hematocrit, which has the potential to increase the risk of venous thromboembolism.

Two large observational studies have reported increased risks of myocardial infarction, stroke, and death in men taking testosterone, compared with nonusers, but the study designs have been widely criticized, Dr. Hudson and coauthors say in their article.  

A placebo-controlled trial was stopped early by its data- and safety-monitoring board following increased cardiovascular events in men aged 65 and older who received 6 months of testosterone. Other controlled trials have not observed these effects, but none was sufficiently powered.
 

Meta-analysis results

Dr. Hudson and colleagues performed a meta-analysis of 35 trials in 5,601 men aged 18 years and older with low baseline testosterone (≤ 350 nmol/dL) who had been randomized to testosterone replacement therapy or placebo for at least 3 months, for which there were data on mortality, stroke, and cardiovascular outcomes.

The men were a mean age of 65, had a mean body mass index of 30 kg/m², and most (88%) were White. A quarter had angina, 8% had a previous myocardial infarction, and 27% had diabetes. 

Cardiovascular and cerebrovascular outcomes were not primary outcomes.

During a mean follow-up of 9.5 months, in the 13 trials that provided this information, the rate of cardiovascular events was similar in the men who received testosterone (120/1,601, 7.5%) compared with those who received placebo (110/1,519, 7.2%).

In the 14 trials that provided this information, fewer deaths were reported during testosterone treatment (6/1,621, 0.4%) than during placebo treatment (12/1,537, 0.8%), but these numbers were too small to establish whether testosterone reduced mortality risk.

The most common cardiovascular events were arrhythmia, followed by coronary heart disease, heart failure, and myocardial infarction.

Patient age, baseline testosterone, smoking status, or diabetes status were not associated with cardiovascular risk.

The only detected adverse effects were edema and a modest lowering of HDL cholesterol.

“Men who develop sexual dysfunction, unexplained anemia, or osteoporosis should be tested for low testosterone,” senior author of the meta-analysis Dr. Jayasena said in an email to this news organization.

However, Dr. Jayasena added, “Mass screening for testosterone has no benefit in asymptomatic men.”

“Older men may still benefit from testosterone, but only if they have the clinical features [of hypogonadism] and low testosterone levels,” he concluded.  

The current study is supported by the Health Technology Assessment program of the National Institute for Health Research. The TRAVERSE trial is sponsored by AbbVie. Dr. Jayasena has reported receiving research grants from LogixX Pharma. Dr. Hudson has reported no relevant financial relationships. Disclosures for the other authors are listed in the article. Dr. Michos has reported receiving support from the Amato Fund in Women’s Cardiovascular Health at Johns Hopkins School of Medicine and serving on medical advisory boards for Novartis, Esperion, Amarin, and AstraZeneca outside the submitted work. Dr. Budoff has reported receiving grant support from General Electric.
 

A version of this article first appeared on Medscape.com.

Despite a new meta-analysis claiming to show that testosterone replacement therapy for men with hypogonadism does not increase the risk of cardiovascular outcomes such as myocardial infarction or stroke, experts say the jury is still out.

A more definitive answer for cardiovascular safety of testosterone therapy will come from the TRAVERSE dedicated cardiovascular outcome trial, sponsored by AbbVie, which will have up to 5 years of follow-up, with results expected later this year.

The current meta-analysis by Jemma Hudson of Aberdeen (Scotland) University and colleagues was published online in The Lancet Healthy Longevity. The work will also be presented June 13 at ENDO 2022, the Endocrine Society’s annual meeting in Atlanta, Georgia, by senior author Channa Y. Jayasena, MD, PhD.

In 2014, the U.S. Food and Drug Administration mandated a label on testosterone products warning of possible increased cardiovascular risks and to reserve the therapy for symptomatic hypogonadism only. In contrast, the European Medicines Agency concluded that when hypogonadism is properly diagnosed and managed, there is currently no clear, consistent evidence that testosterone therapy causes increased cardiovascular risk.

To address this uncertainty, Dr. Hudson and colleagues formed a global collaborative to obtain individual patient data on cardiovascular outcomes from randomized controlled trials of testosterone therapy for men with hypogonadism.

They pooled data from 35 trials published from 1992 to Aug. 27, 2018, including 17 trials (3,431 patients) for which the researchers obtained patient-level data. The individual trials were 3-12 months long, except for one 3-year trial.

During a mean follow-up of 9.5 months, there was no significant increase in cardiovascular outcomes in men randomized to testosterone therapy versus placebo (odds ratio, 1.07; P = .62), nor were there any significantly increased risks of death, stroke, or different types of cardiovascular outcome, although those numbers were small.  

This is “the most comprehensive study to date investigating the safety of testosterone treatment of hypogonadism,” according to the researchers. “The current results provide some reassurance about the short-term to medium-term safety of testosterone to treat male hypogonadism,” they conclude.

However, they also acknowledge that “long-term data are needed to fully evaluate the safety of testosterone.”

Erin D. Michos, MD, coauthor of an accompanying editorial, told this news organization, “This study doesn’t say to me that low testosterone necessarily needs to be treated. It’s still not indicated in people just for a low number [for blood testosterone] with less-severe symptoms. It really comes down to each individual person, how symptomatic they are, and their cardiovascular risk.”

‘Trial is not definitive’

Dr. Michos is not the only person to be skeptical. Together with Steven Nissen, MD, an investigator for the TRAVERSE trial, she agrees that this new evidence is not yet decisive, largely because the individual trials in the meta-analysis were short and not designed as cardiovascular outcome trials.

Dr. Nissen, a cardiologist at Cleveland Clinic, added that the individual trials were heterogeneous, with “very few real cardiovascular events,” so the meta-analysis “is not definitive,” he said in an interview.

While this meta-analysis “that pooled together a lot of smaller studies is reassuring that there’s no signal of harm, it’s really inconclusive because the follow-up was really short – a mean of only 9.5 months – and you really need a larger study with longer follow up to be more conclusive,” Dr. Michos noted.

“We should have more data soon” from TRAVERSE, said Dr. Michos, from the division of cardiology, Johns Hopkins University, Baltimore, who is not involved with that study.

Meanwhile, “I don’t think [this analysis] changes the current recommendations,” she said.

“We should continue to use caution as indicated by the FDA label and only use testosterone therapy selectively in people who have true symptoms of hypogonadism,” and be cautious about using it particularly in men at higher cardiovascular risk because of family history or known personal heart disease.

On the other hand, the meta-analysis did not show harm, she noted, “so we don’t necessarily need to pull patients off therapy if they are already taking it. But I wouldn’t right now just start new patients on it unless they had a strong indication.”

“Certainly, great caution is advised regarding the use of testosterone replacement therapy in people with established atherosclerosis due to the findings of plaque progression in the testosterone trials and the excess cardiovascular events observed in the TOM trial, write Dr. Michos and fellow editorialist Matthew J. Budoff, MD, of University of California, Los Angeles, in their editorial.
 

Earlier data inconclusive

Testosterone concentrations progressively decline in men with advancing age, at about 2% per year, Dr. Michos and Dr. Budoff write. In addition, men with obesity or with diabetes have low levels of testosterone, Dr. Michos noted.

Low testosterone blood levels have been associated with insulin resistance, inflammation, dyslipidemia, and atherosclerosis. Testosterone replacement therapy has been used to increase libido, improve erectile dysfunction, and boost energy levels, mood, and muscle strength.

But it is well known that testosterone increases hematocrit, which has the potential to increase the risk of venous thromboembolism.

Two large observational studies have reported increased risks of myocardial infarction, stroke, and death in men taking testosterone, compared with nonusers, but the study designs have been widely criticized, Dr. Hudson and coauthors say in their article.  

A placebo-controlled trial was stopped early by its data- and safety-monitoring board following increased cardiovascular events in men aged 65 and older who received 6 months of testosterone. Other controlled trials have not observed these effects, but none was sufficiently powered.
 

Meta-analysis results

Dr. Hudson and colleagues performed a meta-analysis of 35 trials in 5,601 men aged 18 years and older with low baseline testosterone (≤ 350 nmol/dL) who had been randomized to testosterone replacement therapy or placebo for at least 3 months, for which there were data on mortality, stroke, and cardiovascular outcomes.

The men were a mean age of 65, had a mean body mass index of 30 kg/m², and most (88%) were White. A quarter had angina, 8% had a previous myocardial infarction, and 27% had diabetes. 

Cardiovascular and cerebrovascular outcomes were not primary outcomes.

During a mean follow-up of 9.5 months, in the 13 trials that provided this information, the rate of cardiovascular events was similar in the men who received testosterone (120/1,601, 7.5%) compared with those who received placebo (110/1,519, 7.2%).

In the 14 trials that provided this information, fewer deaths were reported during testosterone treatment (6/1,621, 0.4%) than during placebo treatment (12/1,537, 0.8%), but these numbers were too small to establish whether testosterone reduced mortality risk.

The most common cardiovascular events were arrhythmia, followed by coronary heart disease, heart failure, and myocardial infarction.

Patient age, baseline testosterone, smoking status, or diabetes status were not associated with cardiovascular risk.

The only detected adverse effects were edema and a modest lowering of HDL cholesterol.

“Men who develop sexual dysfunction, unexplained anemia, or osteoporosis should be tested for low testosterone,” senior author of the meta-analysis Dr. Jayasena said in an email to this news organization.

However, Dr. Jayasena added, “Mass screening for testosterone has no benefit in asymptomatic men.”

“Older men may still benefit from testosterone, but only if they have the clinical features [of hypogonadism] and low testosterone levels,” he concluded.  

The current study is supported by the Health Technology Assessment program of the National Institute for Health Research. The TRAVERSE trial is sponsored by AbbVie. Dr. Jayasena has reported receiving research grants from LogixX Pharma. Dr. Hudson has reported no relevant financial relationships. Disclosures for the other authors are listed in the article. Dr. Michos has reported receiving support from the Amato Fund in Women’s Cardiovascular Health at Johns Hopkins School of Medicine and serving on medical advisory boards for Novartis, Esperion, Amarin, and AstraZeneca outside the submitted work. Dr. Budoff has reported receiving grant support from General Electric.
 

A version of this article first appeared on Medscape.com.

Despite a new meta-analysis claiming to show that testosterone replacement therapy for men with hypogonadism does not increase the risk of cardiovascular outcomes such as myocardial infarction or stroke, experts say the jury is still out.

A more definitive answer for cardiovascular safety of testosterone therapy will come from the TRAVERSE dedicated cardiovascular outcome trial, sponsored by AbbVie, which will have up to 5 years of follow-up, with results expected later this year.

The current meta-analysis by Jemma Hudson of Aberdeen (Scotland) University and colleagues was published online in The Lancet Healthy Longevity. The work will also be presented June 13 at ENDO 2022, the Endocrine Society’s annual meeting in Atlanta, Georgia, by senior author Channa Y. Jayasena, MD, PhD.

In 2014, the U.S. Food and Drug Administration mandated a label on testosterone products warning of possible increased cardiovascular risks and to reserve the therapy for symptomatic hypogonadism only. In contrast, the European Medicines Agency concluded that when hypogonadism is properly diagnosed and managed, there is currently no clear, consistent evidence that testosterone therapy causes increased cardiovascular risk.

To address this uncertainty, Dr. Hudson and colleagues formed a global collaborative to obtain individual patient data on cardiovascular outcomes from randomized controlled trials of testosterone therapy for men with hypogonadism.

They pooled data from 35 trials published from 1992 to Aug. 27, 2018, including 17 trials (3,431 patients) for which the researchers obtained patient-level data. The individual trials were 3-12 months long, except for one 3-year trial.

During a mean follow-up of 9.5 months, there was no significant increase in cardiovascular outcomes in men randomized to testosterone therapy versus placebo (odds ratio, 1.07; P = .62), nor were there any significantly increased risks of death, stroke, or different types of cardiovascular outcome, although those numbers were small.  

This is “the most comprehensive study to date investigating the safety of testosterone treatment of hypogonadism,” according to the researchers. “The current results provide some reassurance about the short-term to medium-term safety of testosterone to treat male hypogonadism,” they conclude.

However, they also acknowledge that “long-term data are needed to fully evaluate the safety of testosterone.”

Erin D. Michos, MD, coauthor of an accompanying editorial, told this news organization, “This study doesn’t say to me that low testosterone necessarily needs to be treated. It’s still not indicated in people just for a low number [for blood testosterone] with less-severe symptoms. It really comes down to each individual person, how symptomatic they are, and their cardiovascular risk.”

‘Trial is not definitive’

Dr. Michos is not the only person to be skeptical. Together with Steven Nissen, MD, an investigator for the TRAVERSE trial, she agrees that this new evidence is not yet decisive, largely because the individual trials in the meta-analysis were short and not designed as cardiovascular outcome trials.

Dr. Nissen, a cardiologist at Cleveland Clinic, added that the individual trials were heterogeneous, with “very few real cardiovascular events,” so the meta-analysis “is not definitive,” he said in an interview.

While this meta-analysis “that pooled together a lot of smaller studies is reassuring that there’s no signal of harm, it’s really inconclusive because the follow-up was really short – a mean of only 9.5 months – and you really need a larger study with longer follow up to be more conclusive,” Dr. Michos noted.

“We should have more data soon” from TRAVERSE, said Dr. Michos, from the division of cardiology, Johns Hopkins University, Baltimore, who is not involved with that study.

Meanwhile, “I don’t think [this analysis] changes the current recommendations,” she said.

“We should continue to use caution as indicated by the FDA label and only use testosterone therapy selectively in people who have true symptoms of hypogonadism,” and be cautious about using it particularly in men at higher cardiovascular risk because of family history or known personal heart disease.

On the other hand, the meta-analysis did not show harm, she noted, “so we don’t necessarily need to pull patients off therapy if they are already taking it. But I wouldn’t right now just start new patients on it unless they had a strong indication.”

“Certainly, great caution is advised regarding the use of testosterone replacement therapy in people with established atherosclerosis due to the findings of plaque progression in the testosterone trials and the excess cardiovascular events observed in the TOM trial, write Dr. Michos and fellow editorialist Matthew J. Budoff, MD, of University of California, Los Angeles, in their editorial.
 

Earlier data inconclusive

Testosterone concentrations progressively decline in men with advancing age, at about 2% per year, Dr. Michos and Dr. Budoff write. In addition, men with obesity or with diabetes have low levels of testosterone, Dr. Michos noted.

Low testosterone blood levels have been associated with insulin resistance, inflammation, dyslipidemia, and atherosclerosis. Testosterone replacement therapy has been used to increase libido, improve erectile dysfunction, and boost energy levels, mood, and muscle strength.

But it is well known that testosterone increases hematocrit, which has the potential to increase the risk of venous thromboembolism.

Two large observational studies have reported increased risks of myocardial infarction, stroke, and death in men taking testosterone, compared with nonusers, but the study designs have been widely criticized, Dr. Hudson and coauthors say in their article.  

A placebo-controlled trial was stopped early by its data- and safety-monitoring board following increased cardiovascular events in men aged 65 and older who received 6 months of testosterone. Other controlled trials have not observed these effects, but none was sufficiently powered.
 

Meta-analysis results

Dr. Hudson and colleagues performed a meta-analysis of 35 trials in 5,601 men aged 18 years and older with low baseline testosterone (≤ 350 nmol/dL) who had been randomized to testosterone replacement therapy or placebo for at least 3 months, for which there were data on mortality, stroke, and cardiovascular outcomes.

The men were a mean age of 65, had a mean body mass index of 30 kg/m², and most (88%) were White. A quarter had angina, 8% had a previous myocardial infarction, and 27% had diabetes. 

Cardiovascular and cerebrovascular outcomes were not primary outcomes.

During a mean follow-up of 9.5 months, in the 13 trials that provided this information, the rate of cardiovascular events was similar in the men who received testosterone (120/1,601, 7.5%) compared with those who received placebo (110/1,519, 7.2%).

In the 14 trials that provided this information, fewer deaths were reported during testosterone treatment (6/1,621, 0.4%) than during placebo treatment (12/1,537, 0.8%), but these numbers were too small to establish whether testosterone reduced mortality risk.

The most common cardiovascular events were arrhythmia, followed by coronary heart disease, heart failure, and myocardial infarction.

Patient age, baseline testosterone, smoking status, or diabetes status were not associated with cardiovascular risk.

The only detected adverse effects were edema and a modest lowering of HDL cholesterol.

“Men who develop sexual dysfunction, unexplained anemia, or osteoporosis should be tested for low testosterone,” senior author of the meta-analysis Dr. Jayasena said in an email to this news organization.

However, Dr. Jayasena added, “Mass screening for testosterone has no benefit in asymptomatic men.”

“Older men may still benefit from testosterone, but only if they have the clinical features [of hypogonadism] and low testosterone levels,” he concluded.  

The current study is supported by the Health Technology Assessment program of the National Institute for Health Research. The TRAVERSE trial is sponsored by AbbVie. Dr. Jayasena has reported receiving research grants from LogixX Pharma. Dr. Hudson has reported no relevant financial relationships. Disclosures for the other authors are listed in the article. Dr. Michos has reported receiving support from the Amato Fund in Women’s Cardiovascular Health at Johns Hopkins School of Medicine and serving on medical advisory boards for Novartis, Esperion, Amarin, and AstraZeneca outside the submitted work. Dr. Budoff has reported receiving grant support from General Electric.
 

A version of this article first appeared on Medscape.com.

The 1-year results of the Harmony transcatheter pulmonary valve to treat severe pulmonary regurgitation have shown a high rate of eliminating or reducing the degree of symptoms as well as freedom from endocarditis, sustained ventricular tachycardia, and the need for further interventions.

“Simply put, the good news is no endocarditis,” said Daniel S. Levi, MD, in presenting results from three different studies with 108 patients who received three different iterations of the device at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

courtesy University of California, Los Angeles

“Endocarditis has been an issue for us in the pulmonary position; we have yet to have an endocarditis in these patients in 1 year,” he stressed.

The studies evaluated three different versions of the Harmony valve: TPV22 (42 patients), the first version with a 22-mm diameter; the Clinical TPV25 (17 patients), the first iteration of a 25 mm–wide device that has since been discontinued; and the modified TPV25 (45 patients), the second version of the 25-mm valve. The three studies are the early feasibility study of the TPV22, the continued-access study of the TPV22 and the mTPV25, and the pivotal study that included all three versions.

At baseline, 89% of patients had severe and 11% had moderate pulmonary regurgitation (PR). At 1 year, 92% had none or trace PR, 3% had mild PR, and 4% moderate disease.  

Dr. Levi said the device “speaks for itself” in the results he presented. They include no deaths, no heart attacks, and no pulmonary thromboembolism. Other key outcomes include:

• One major stent fracture in one of the early feasibility study patients at 1-month follow-up.
• Four explants, with two in the discontinued cTPV25 and two with the TPV22 in the early-feasibility study.
• Four reinterventions, two with the discontinued cTPV25 and two valve-in-valve procedures with the mTPV25 in the continued-access study, one with stent placement in the right ventricular outflow tract.

Dr. Levi and coinvestigators also performed a breakdown of 1-year outcomes – freedom from PR, stenosis, and interventions – by device: 95.1% for TPV22; 89.7% for mTPV25; and 73.3% for the discontinued cTPV25.

Although the valve is indicated for adolescents and adults, most of the patients in the three studies were adults, with an average weight of 165 pounds (75 kg) who have had PR for decades, said Dr. Levi, an interventional pediatric cardiologist at the University of California, Los Angeles. “With a device like this we are hopefully shifting to treating that a little bit earlier, but fortunately we don’t usually need to treat it before puberty.” The 25-mm TPV gives “a really nice landing zone” for future valve placement. “The goal is to keep patients out of the operating room for at least a few decades if not their whole lives,” he said.

Dr. Levi said the Harmony investigators will follow outcomes with the 22- and modified 25-mm Harmony valves, both of which remain commercially available, out to 10 years.

The study represents the first collective cohort evaluating the Harmony device across the early feasibility, continued access and pivotal studies, said Brian Morray, MD. “It’s important that people understand that evolution and how that impacts the way we look at outcomes, because when you aggregate the data, particularly for the TPV25, some of the procedural outcomes and the adverse events are no longer really reflective in the current time frame.”

These Harmony results “represent another big step in the evolution of interventional cardiology and will be up there with development of the Melody valve and the utility and the use of the Sapien valve in the pulmonary position,” said Dr. Morray, an associate professor of pediatrics at the University of Washington, Seattle, and an interventional cardiologist at Seattle Children’s Hospital.

Dr. Levi disclosed he is a consultant to Medtronic and Edwards Lifesciences. Dr. Morray disclosed he is a clinical proctor for Abbott and a consultant to Medtronic, but not for the Harmony device.
 

The 1-year results of the Harmony transcatheter pulmonary valve to treat severe pulmonary regurgitation have shown a high rate of eliminating or reducing the degree of symptoms as well as freedom from endocarditis, sustained ventricular tachycardia, and the need for further interventions.

“Simply put, the good news is no endocarditis,” said Daniel S. Levi, MD, in presenting results from three different studies with 108 patients who received three different iterations of the device at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

courtesy University of California, Los Angeles

“Endocarditis has been an issue for us in the pulmonary position; we have yet to have an endocarditis in these patients in 1 year,” he stressed.

The studies evaluated three different versions of the Harmony valve: TPV22 (42 patients), the first version with a 22-mm diameter; the Clinical TPV25 (17 patients), the first iteration of a 25 mm–wide device that has since been discontinued; and the modified TPV25 (45 patients), the second version of the 25-mm valve. The three studies are the early feasibility study of the TPV22, the continued-access study of the TPV22 and the mTPV25, and the pivotal study that included all three versions.

At baseline, 89% of patients had severe and 11% had moderate pulmonary regurgitation (PR). At 1 year, 92% had none or trace PR, 3% had mild PR, and 4% moderate disease.  

Dr. Levi said the device “speaks for itself” in the results he presented. They include no deaths, no heart attacks, and no pulmonary thromboembolism. Other key outcomes include:

• One major stent fracture in one of the early feasibility study patients at 1-month follow-up.
• Four explants, with two in the discontinued cTPV25 and two with the TPV22 in the early-feasibility study.
• Four reinterventions, two with the discontinued cTPV25 and two valve-in-valve procedures with the mTPV25 in the continued-access study, one with stent placement in the right ventricular outflow tract.

Dr. Levi and coinvestigators also performed a breakdown of 1-year outcomes – freedom from PR, stenosis, and interventions – by device: 95.1% for TPV22; 89.7% for mTPV25; and 73.3% for the discontinued cTPV25.

Although the valve is indicated for adolescents and adults, most of the patients in the three studies were adults, with an average weight of 165 pounds (75 kg) who have had PR for decades, said Dr. Levi, an interventional pediatric cardiologist at the University of California, Los Angeles. “With a device like this we are hopefully shifting to treating that a little bit earlier, but fortunately we don’t usually need to treat it before puberty.” The 25-mm TPV gives “a really nice landing zone” for future valve placement. “The goal is to keep patients out of the operating room for at least a few decades if not their whole lives,” he said.

Dr. Levi said the Harmony investigators will follow outcomes with the 22- and modified 25-mm Harmony valves, both of which remain commercially available, out to 10 years.

The study represents the first collective cohort evaluating the Harmony device across the early feasibility, continued access and pivotal studies, said Brian Morray, MD. “It’s important that people understand that evolution and how that impacts the way we look at outcomes, because when you aggregate the data, particularly for the TPV25, some of the procedural outcomes and the adverse events are no longer really reflective in the current time frame.”

These Harmony results “represent another big step in the evolution of interventional cardiology and will be up there with development of the Melody valve and the utility and the use of the Sapien valve in the pulmonary position,” said Dr. Morray, an associate professor of pediatrics at the University of Washington, Seattle, and an interventional cardiologist at Seattle Children’s Hospital.

Dr. Levi disclosed he is a consultant to Medtronic and Edwards Lifesciences. Dr. Morray disclosed he is a clinical proctor for Abbott and a consultant to Medtronic, but not for the Harmony device.
 

The 1-year results of the Harmony transcatheter pulmonary valve to treat severe pulmonary regurgitation have shown a high rate of eliminating or reducing the degree of symptoms as well as freedom from endocarditis, sustained ventricular tachycardia, and the need for further interventions.

“Simply put, the good news is no endocarditis,” said Daniel S. Levi, MD, in presenting results from three different studies with 108 patients who received three different iterations of the device at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

courtesy University of California, Los Angeles

“Endocarditis has been an issue for us in the pulmonary position; we have yet to have an endocarditis in these patients in 1 year,” he stressed.

The studies evaluated three different versions of the Harmony valve: TPV22 (42 patients), the first version with a 22-mm diameter; the Clinical TPV25 (17 patients), the first iteration of a 25 mm–wide device that has since been discontinued; and the modified TPV25 (45 patients), the second version of the 25-mm valve. The three studies are the early feasibility study of the TPV22, the continued-access study of the TPV22 and the mTPV25, and the pivotal study that included all three versions.

At baseline, 89% of patients had severe and 11% had moderate pulmonary regurgitation (PR). At 1 year, 92% had none or trace PR, 3% had mild PR, and 4% moderate disease.  

Dr. Levi said the device “speaks for itself” in the results he presented. They include no deaths, no heart attacks, and no pulmonary thromboembolism. Other key outcomes include:

• One major stent fracture in one of the early feasibility study patients at 1-month follow-up.
• Four explants, with two in the discontinued cTPV25 and two with the TPV22 in the early-feasibility study.
• Four reinterventions, two with the discontinued cTPV25 and two valve-in-valve procedures with the mTPV25 in the continued-access study, one with stent placement in the right ventricular outflow tract.

Dr. Levi and coinvestigators also performed a breakdown of 1-year outcomes – freedom from PR, stenosis, and interventions – by device: 95.1% for TPV22; 89.7% for mTPV25; and 73.3% for the discontinued cTPV25.

Although the valve is indicated for adolescents and adults, most of the patients in the three studies were adults, with an average weight of 165 pounds (75 kg) who have had PR for decades, said Dr. Levi, an interventional pediatric cardiologist at the University of California, Los Angeles. “With a device like this we are hopefully shifting to treating that a little bit earlier, but fortunately we don’t usually need to treat it before puberty.” The 25-mm TPV gives “a really nice landing zone” for future valve placement. “The goal is to keep patients out of the operating room for at least a few decades if not their whole lives,” he said.

Dr. Levi said the Harmony investigators will follow outcomes with the 22- and modified 25-mm Harmony valves, both of which remain commercially available, out to 10 years.

The study represents the first collective cohort evaluating the Harmony device across the early feasibility, continued access and pivotal studies, said Brian Morray, MD. “It’s important that people understand that evolution and how that impacts the way we look at outcomes, because when you aggregate the data, particularly for the TPV25, some of the procedural outcomes and the adverse events are no longer really reflective in the current time frame.”

These Harmony results “represent another big step in the evolution of interventional cardiology and will be up there with development of the Melody valve and the utility and the use of the Sapien valve in the pulmonary position,” said Dr. Morray, an associate professor of pediatrics at the University of Washington, Seattle, and an interventional cardiologist at Seattle Children’s Hospital.

Dr. Levi disclosed he is a consultant to Medtronic and Edwards Lifesciences. Dr. Morray disclosed he is a clinical proctor for Abbott and a consultant to Medtronic, but not for the Harmony device.
 

As it gears up for the first in-person scientific sessions for 3 years, the American Diabetes Association has issued an addendum to its most recent annual clinical practice recommendations published in December 2021, the 2022 Standards of Medical Care in Diabetes, based on recent trial evidence and consensus.

The update informs clinicians about:

• The effect of the nonsteroidal mineralocorticoid antagonist (Kerendia) on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease.
• The effect of a sodium-glucose cotransporter 2 (SGLT2) inhibitor on heart failure and renal outcomes in patients with type 2 diabetes.

The National Kidney Foundation and the American Society of Nephrology Task Force recommendation to remove race in the formula for calculating estimated glomerular filtration rate (eGFR).

Checking with Dr Gabbay -- RM 08/16

“This is the fifth year that we are able to update the Standards of Care after it has been published through our Living Standards of Care updates, making it possible to give diabetes care providers the most important information and the latest evidence relevant to their practice,” Robert A. Gabbay, MD, PhD, ADA chief scientific and medical officer, said in a press release from the organization.

The addendum, entitled, “Living Standards of Care,” updates Section 10, “Cardiovascular Disease and Risk Management,” and Section 11, “Chronic Kidney Disease and Risk Management” of the 2022 Standards of Medical Care in Diabetes. 

The amendments were approved by the ADA Professional Practice Committee, which is responsible for developing the Standards of Care. The American College of Cardiology reviewed and endorsed the section on CVD and risk management.

The Living Standards Update was published online in Diabetes Care.
 

CVD and risk management

In the Addendum to Section 10, “Cardiovascular Disease and Risk Management,” the committee writes:

• “For patients with type 2 diabetes and chronic kidney disease treated with maximum tolerated doses of ACE inhibitors or angiotensin receptor blockers, addition of finerenone should be considered to improve cardiovascular outcomes and reduce the risk of chronic kidney disease progression. A”
• “Patients with type 2 diabetes and chronic kidney disease should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of chronic kidney disease progression.”
• “In patients with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor [with proven benefit in this patient population] is recommended to reduce risk of worsening heart failure, hospitalizations for heart failure, and cardiovascular death. ”

In the section “Statin Treatment,” the addendum no longer states that “a prospective trial of a newer fibrate ... is ongoing,” because that trial investigating pemafibrate (Kowa), a novel selective peroxisome proliferator-activated receptor alpha modulator (or fibrate), has been discontinued.
 

Chronic kidney disease and risk management

In the Addendum to Section 11, “Chronic Kidney Disease and Risk Management,” the committee writes: 

• “Traditionally, eGFR is calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is preferred. ... Historically, a correction factor for muscle mass was included in a modified equation for African Americans; however, due to various issues with inequities, it was decided to the equation such that it applies to all. Hence, a committee was convened, resulting in the recommendation for immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the U.S.” (This is based on an National Kidney Foundation and American Society of Nephrology Task Force recommendation.)
• “Additionally, increased use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone.” 

Evidence from clinical trials

The update is based on findings from the following clinical trials:

• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD)
• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD)
• FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD
• Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved)
• Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients with PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF)
• Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT).

A version of this article first appeared on Medscape.com.

As it gears up for the first in-person scientific sessions for 3 years, the American Diabetes Association has issued an addendum to its most recent annual clinical practice recommendations published in December 2021, the 2022 Standards of Medical Care in Diabetes, based on recent trial evidence and consensus.

The update informs clinicians about:

• The effect of the nonsteroidal mineralocorticoid antagonist (Kerendia) on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease.
• The effect of a sodium-glucose cotransporter 2 (SGLT2) inhibitor on heart failure and renal outcomes in patients with type 2 diabetes.

The National Kidney Foundation and the American Society of Nephrology Task Force recommendation to remove race in the formula for calculating estimated glomerular filtration rate (eGFR).

Checking with Dr Gabbay -- RM 08/16

“This is the fifth year that we are able to update the Standards of Care after it has been published through our Living Standards of Care updates, making it possible to give diabetes care providers the most important information and the latest evidence relevant to their practice,” Robert A. Gabbay, MD, PhD, ADA chief scientific and medical officer, said in a press release from the organization.

The addendum, entitled, “Living Standards of Care,” updates Section 10, “Cardiovascular Disease and Risk Management,” and Section 11, “Chronic Kidney Disease and Risk Management” of the 2022 Standards of Medical Care in Diabetes. 

The amendments were approved by the ADA Professional Practice Committee, which is responsible for developing the Standards of Care. The American College of Cardiology reviewed and endorsed the section on CVD and risk management.

The Living Standards Update was published online in Diabetes Care.
 

CVD and risk management

In the Addendum to Section 10, “Cardiovascular Disease and Risk Management,” the committee writes:

• “For patients with type 2 diabetes and chronic kidney disease treated with maximum tolerated doses of ACE inhibitors or angiotensin receptor blockers, addition of finerenone should be considered to improve cardiovascular outcomes and reduce the risk of chronic kidney disease progression. A”
• “Patients with type 2 diabetes and chronic kidney disease should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of chronic kidney disease progression.”
• “In patients with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor [with proven benefit in this patient population] is recommended to reduce risk of worsening heart failure, hospitalizations for heart failure, and cardiovascular death. ”

In the section “Statin Treatment,” the addendum no longer states that “a prospective trial of a newer fibrate ... is ongoing,” because that trial investigating pemafibrate (Kowa), a novel selective peroxisome proliferator-activated receptor alpha modulator (or fibrate), has been discontinued.
 

Chronic kidney disease and risk management

In the Addendum to Section 11, “Chronic Kidney Disease and Risk Management,” the committee writes: 

• “Traditionally, eGFR is calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is preferred. ... Historically, a correction factor for muscle mass was included in a modified equation for African Americans; however, due to various issues with inequities, it was decided to the equation such that it applies to all. Hence, a committee was convened, resulting in the recommendation for immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the U.S.” (This is based on an National Kidney Foundation and American Society of Nephrology Task Force recommendation.)
• “Additionally, increased use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone.” 

Evidence from clinical trials

The update is based on findings from the following clinical trials:

• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD)
• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD)
• FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD
• Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved)
• Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients with PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF)
• Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT).

A version of this article first appeared on Medscape.com.

As it gears up for the first in-person scientific sessions for 3 years, the American Diabetes Association has issued an addendum to its most recent annual clinical practice recommendations published in December 2021, the 2022 Standards of Medical Care in Diabetes, based on recent trial evidence and consensus.

The update informs clinicians about:

• The effect of the nonsteroidal mineralocorticoid antagonist (Kerendia) on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease.
• The effect of a sodium-glucose cotransporter 2 (SGLT2) inhibitor on heart failure and renal outcomes in patients with type 2 diabetes.

The National Kidney Foundation and the American Society of Nephrology Task Force recommendation to remove race in the formula for calculating estimated glomerular filtration rate (eGFR).

Checking with Dr Gabbay -- RM 08/16

“This is the fifth year that we are able to update the Standards of Care after it has been published through our Living Standards of Care updates, making it possible to give diabetes care providers the most important information and the latest evidence relevant to their practice,” Robert A. Gabbay, MD, PhD, ADA chief scientific and medical officer, said in a press release from the organization.

The addendum, entitled, “Living Standards of Care,” updates Section 10, “Cardiovascular Disease and Risk Management,” and Section 11, “Chronic Kidney Disease and Risk Management” of the 2022 Standards of Medical Care in Diabetes. 

The amendments were approved by the ADA Professional Practice Committee, which is responsible for developing the Standards of Care. The American College of Cardiology reviewed and endorsed the section on CVD and risk management.

The Living Standards Update was published online in Diabetes Care.
 

CVD and risk management

In the Addendum to Section 10, “Cardiovascular Disease and Risk Management,” the committee writes:

• “For patients with type 2 diabetes and chronic kidney disease treated with maximum tolerated doses of ACE inhibitors or angiotensin receptor blockers, addition of finerenone should be considered to improve cardiovascular outcomes and reduce the risk of chronic kidney disease progression. A”
• “Patients with type 2 diabetes and chronic kidney disease should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of chronic kidney disease progression.”
• “In patients with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor [with proven benefit in this patient population] is recommended to reduce risk of worsening heart failure, hospitalizations for heart failure, and cardiovascular death. ”

In the section “Statin Treatment,” the addendum no longer states that “a prospective trial of a newer fibrate ... is ongoing,” because that trial investigating pemafibrate (Kowa), a novel selective peroxisome proliferator-activated receptor alpha modulator (or fibrate), has been discontinued.
 

Chronic kidney disease and risk management

In the Addendum to Section 11, “Chronic Kidney Disease and Risk Management,” the committee writes: 

• “Traditionally, eGFR is calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is preferred. ... Historically, a correction factor for muscle mass was included in a modified equation for African Americans; however, due to various issues with inequities, it was decided to the equation such that it applies to all. Hence, a committee was convened, resulting in the recommendation for immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the U.S.” (This is based on an National Kidney Foundation and American Society of Nephrology Task Force recommendation.)
• “Additionally, increased use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone.” 

Evidence from clinical trials

The update is based on findings from the following clinical trials:

• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD)
• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD)
• FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD
• Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved)
• Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients with PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF)
• Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT).

A version of this article first appeared on Medscape.com.

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.

Technical and procedural success rates for chronic total occlusion percutaneous coronary intervention (CTO PCI) have increased steadily over the past 6 years, with rates of in-hospital major adverse cardiac events (MACE) declining to the 2%-or-lower range in that time.

“CTO PCI technical and procedural success rates are high and continue to increase over time,” Spyridon Kostantinis, MD said in presenting updated results from the international PROGRESS-CTO registry at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

Courtesy Minneapolis Heart Institute Foundation

“The overall success rate increased from 81.6% in 2018 to 88.1% in 2021,” he added. The overall incidence of in-hospital MACE in that time was “an acceptable” 2.1% without significant changes over that period.

The analysis examined clinical, angiographic and procedural outcomes of 10,249 CTO PCIs performed on 10,019 patients from 63 centers in nine countries during 2016-2021. PROGRESS-CTO stands for Prospective Global Registry for the Study of Chronic Total Occlusion Intervention.

The target CTOs were highly complex, he said, with an average J-CTO (multicenter CTO registry in Japan) score of 2.4 ± 1.3 and PROGRESS-CTO score of 1.3 ± 1. The most common CTO target vessel was the right coronary artery (53%), followed by the left anterior descending artery (26%) and the circumflex artery (19%).

The registry also tracked how characteristics of the CTO PCI procedures themselves changed over time. “The septal and the epicardial collaterals were the most common collaterals used for retrograde crossing, with a decreasing trend for epicardial collaterals over time,” said Dr. Kostantinis, a research fellow at the Minneapolis Heart Institute.

Septal collateral use varied between 64% and 69% of cases from 2016 to 2021, but the share of epicardial collaterals declined from 35% to 22% in that time.

“Over time, the range of antegrade wiring as the final successfully crossing strategy increased from 46% in 2016 to 61% in 2021, with a decrease in antegrade dissection and re-entry (ADR) and no change in the retrograde approach,” Dr. Kostantinis said. The percentage of procedures using ADR as the final crossing strategy declined from 18% in 2016 to 12% in 2021, with the rate of retrograde crossings peaking at 21% in 2016 but leveling off to 18% or 19% in the subsequent years.

“An increasing use in the efficiency of antegrade wiring may reflect an improvement in guidewire retrograde crossing as well as the increasing operator expertise,” Dr. Kostantinis said.

The study also found that contrast volume, air kerma radiation dose, fluoroscopy time, and procedure time declined steadily over time. “The potential explanations for these are using new x-ray systems as well as the use of intravascular imaging,” Dr. Kostantinis said.

In 2020, the rates of technical and procedural success, as well as the number of overall procedures, declined from 2019, while MACE rates ticked upward that year, probably because of the COVID-19 pandemic, Dr. Kostantinis said.

“It is true that we noticed a rise in MACE rate from 1.6% in 2019 to 2.7% in 2020, but in 2021 that decreased again to 1.7%,” he said in an interview. “Another potential explanation is the higher angiographic complexity of CTOs treated during that year (2020) that resulted in more adverse events.”

Previous results from the PROGRESS-CTO registry reported the difference in MACE between 2019 and 2020 was significant (P  = .01). “So, yes, the difference between those 2 years is significant,” Dr. Kostantinis said. However, he noted, the overall trend was not significant, with a P value of .194.

The risk profile of CTO PCI has improved “slowly” over time, said Kirk N. Garratt, MD, but “it’s not yet were it needs to be.”

He added, “Undoubtedly we’ve learned that, without any question, one method for minimizing the risk is to concentrate these cases in the hands of those that do many of them.” As the number of procedures fell – an “embedded” pandemic impact –“I worry that it’s inevitable that complication rates will tick up a bit,” said Dr. Garratt, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del.

By the same token, he added, this situation with regard to CTOs “parallels what’s happening elsewhere in interventional medicine and medicine broadly; numbers are increasing and we’re busy again. In most domains we’re not as busy as we had been prepandemic, and time will allow us to catch up.”

PROGRESS-CTO has received funding from the Joseph F. and Mary M. Fleischhacker Foundation and the Abbott Northwestern Hospital Foundation Innovation Grant.

Dr. Kostantinis has no disclosures. Dr. Garratt is an advisory board member for Abbott.

Technical and procedural success rates for chronic total occlusion percutaneous coronary intervention (CTO PCI) have increased steadily over the past 6 years, with rates of in-hospital major adverse cardiac events (MACE) declining to the 2%-or-lower range in that time.

“CTO PCI technical and procedural success rates are high and continue to increase over time,” Spyridon Kostantinis, MD said in presenting updated results from the international PROGRESS-CTO registry at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

Courtesy Minneapolis Heart Institute Foundation

“The overall success rate increased from 81.6% in 2018 to 88.1% in 2021,” he added. The overall incidence of in-hospital MACE in that time was “an acceptable” 2.1% without significant changes over that period.

The analysis examined clinical, angiographic and procedural outcomes of 10,249 CTO PCIs performed on 10,019 patients from 63 centers in nine countries during 2016-2021. PROGRESS-CTO stands for Prospective Global Registry for the Study of Chronic Total Occlusion Intervention.

The target CTOs were highly complex, he said, with an average J-CTO (multicenter CTO registry in Japan) score of 2.4 ± 1.3 and PROGRESS-CTO score of 1.3 ± 1. The most common CTO target vessel was the right coronary artery (53%), followed by the left anterior descending artery (26%) and the circumflex artery (19%).

The registry also tracked how characteristics of the CTO PCI procedures themselves changed over time. “The septal and the epicardial collaterals were the most common collaterals used for retrograde crossing, with a decreasing trend for epicardial collaterals over time,” said Dr. Kostantinis, a research fellow at the Minneapolis Heart Institute.

Septal collateral use varied between 64% and 69% of cases from 2016 to 2021, but the share of epicardial collaterals declined from 35% to 22% in that time.

“Over time, the range of antegrade wiring as the final successfully crossing strategy increased from 46% in 2016 to 61% in 2021, with a decrease in antegrade dissection and re-entry (ADR) and no change in the retrograde approach,” Dr. Kostantinis said. The percentage of procedures using ADR as the final crossing strategy declined from 18% in 2016 to 12% in 2021, with the rate of retrograde crossings peaking at 21% in 2016 but leveling off to 18% or 19% in the subsequent years.

“An increasing use in the efficiency of antegrade wiring may reflect an improvement in guidewire retrograde crossing as well as the increasing operator expertise,” Dr. Kostantinis said.

The study also found that contrast volume, air kerma radiation dose, fluoroscopy time, and procedure time declined steadily over time. “The potential explanations for these are using new x-ray systems as well as the use of intravascular imaging,” Dr. Kostantinis said.

In 2020, the rates of technical and procedural success, as well as the number of overall procedures, declined from 2019, while MACE rates ticked upward that year, probably because of the COVID-19 pandemic, Dr. Kostantinis said.

“It is true that we noticed a rise in MACE rate from 1.6% in 2019 to 2.7% in 2020, but in 2021 that decreased again to 1.7%,” he said in an interview. “Another potential explanation is the higher angiographic complexity of CTOs treated during that year (2020) that resulted in more adverse events.”

Previous results from the PROGRESS-CTO registry reported the difference in MACE between 2019 and 2020 was significant (P  = .01). “So, yes, the difference between those 2 years is significant,” Dr. Kostantinis said. However, he noted, the overall trend was not significant, with a P value of .194.

The risk profile of CTO PCI has improved “slowly” over time, said Kirk N. Garratt, MD, but “it’s not yet were it needs to be.”

He added, “Undoubtedly we’ve learned that, without any question, one method for minimizing the risk is to concentrate these cases in the hands of those that do many of them.” As the number of procedures fell – an “embedded” pandemic impact –“I worry that it’s inevitable that complication rates will tick up a bit,” said Dr. Garratt, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del.

By the same token, he added, this situation with regard to CTOs “parallels what’s happening elsewhere in interventional medicine and medicine broadly; numbers are increasing and we’re busy again. In most domains we’re not as busy as we had been prepandemic, and time will allow us to catch up.”

PROGRESS-CTO has received funding from the Joseph F. and Mary M. Fleischhacker Foundation and the Abbott Northwestern Hospital Foundation Innovation Grant.

Dr. Kostantinis has no disclosures. Dr. Garratt is an advisory board member for Abbott.

Technical and procedural success rates for chronic total occlusion percutaneous coronary intervention (CTO PCI) have increased steadily over the past 6 years, with rates of in-hospital major adverse cardiac events (MACE) declining to the 2%-or-lower range in that time.

“CTO PCI technical and procedural success rates are high and continue to increase over time,” Spyridon Kostantinis, MD said in presenting updated results from the international PROGRESS-CTO registry at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

Courtesy Minneapolis Heart Institute Foundation

“The overall success rate increased from 81.6% in 2018 to 88.1% in 2021,” he added. The overall incidence of in-hospital MACE in that time was “an acceptable” 2.1% without significant changes over that period.

The analysis examined clinical, angiographic and procedural outcomes of 10,249 CTO PCIs performed on 10,019 patients from 63 centers in nine countries during 2016-2021. PROGRESS-CTO stands for Prospective Global Registry for the Study of Chronic Total Occlusion Intervention.

The target CTOs were highly complex, he said, with an average J-CTO (multicenter CTO registry in Japan) score of 2.4 ± 1.3 and PROGRESS-CTO score of 1.3 ± 1. The most common CTO target vessel was the right coronary artery (53%), followed by the left anterior descending artery (26%) and the circumflex artery (19%).

The registry also tracked how characteristics of the CTO PCI procedures themselves changed over time. “The septal and the epicardial collaterals were the most common collaterals used for retrograde crossing, with a decreasing trend for epicardial collaterals over time,” said Dr. Kostantinis, a research fellow at the Minneapolis Heart Institute.

Septal collateral use varied between 64% and 69% of cases from 2016 to 2021, but the share of epicardial collaterals declined from 35% to 22% in that time.

“Over time, the range of antegrade wiring as the final successfully crossing strategy increased from 46% in 2016 to 61% in 2021, with a decrease in antegrade dissection and re-entry (ADR) and no change in the retrograde approach,” Dr. Kostantinis said. The percentage of procedures using ADR as the final crossing strategy declined from 18% in 2016 to 12% in 2021, with the rate of retrograde crossings peaking at 21% in 2016 but leveling off to 18% or 19% in the subsequent years.

“An increasing use in the efficiency of antegrade wiring may reflect an improvement in guidewire retrograde crossing as well as the increasing operator expertise,” Dr. Kostantinis said.

The study also found that contrast volume, air kerma radiation dose, fluoroscopy time, and procedure time declined steadily over time. “The potential explanations for these are using new x-ray systems as well as the use of intravascular imaging,” Dr. Kostantinis said.

In 2020, the rates of technical and procedural success, as well as the number of overall procedures, declined from 2019, while MACE rates ticked upward that year, probably because of the COVID-19 pandemic, Dr. Kostantinis said.

“It is true that we noticed a rise in MACE rate from 1.6% in 2019 to 2.7% in 2020, but in 2021 that decreased again to 1.7%,” he said in an interview. “Another potential explanation is the higher angiographic complexity of CTOs treated during that year (2020) that resulted in more adverse events.”

Previous results from the PROGRESS-CTO registry reported the difference in MACE between 2019 and 2020 was significant (P  = .01). “So, yes, the difference between those 2 years is significant,” Dr. Kostantinis said. However, he noted, the overall trend was not significant, with a P value of .194.

The risk profile of CTO PCI has improved “slowly” over time, said Kirk N. Garratt, MD, but “it’s not yet were it needs to be.”

He added, “Undoubtedly we’ve learned that, without any question, one method for minimizing the risk is to concentrate these cases in the hands of those that do many of them.” As the number of procedures fell – an “embedded” pandemic impact –“I worry that it’s inevitable that complication rates will tick up a bit,” said Dr. Garratt, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del.

By the same token, he added, this situation with regard to CTOs “parallels what’s happening elsewhere in interventional medicine and medicine broadly; numbers are increasing and we’re busy again. In most domains we’re not as busy as we had been prepandemic, and time will allow us to catch up.”

PROGRESS-CTO has received funding from the Joseph F. and Mary M. Fleischhacker Foundation and the Abbott Northwestern Hospital Foundation Innovation Grant.

Dr. Kostantinis has no disclosures. Dr. Garratt is an advisory board member for Abbott.

Spending more time doing light-intensity activities and less time being sedentary was associated with a reduced risk for first stroke in a population-based study of middle aged and older adults.

The study also found relatively short periods of moderate to vigorous exercise were associated with reduced stroke risk.

“Our results suggest there are a number of ways to reduce stroke risk simply by moving about,” said lead author Steven P. Hooker, PhD, San Diego State University. “This could be with short periods of moderate to vigorous activity each day, longer periods of light activity, or just sedentary for shorter periods of time. All these things can make a difference.”

Dr. Hooker explained that, while it has been found previously that moderate to vigorous exercise reduces stroke risk, this study gives more information on light-intensity activities and sedentary behavior and the risk of stroke.

“Our results suggest that you don’t have to be a chronic exerciser to reduce stroke risk. Replacing sedentary time with light-intensity activity will be beneficial. Just go for a short walk, get up from your desk and move around the house at regular intervals. That can help to reduce stroke risk,” Dr. Hooker said.  

“Our message is basically to sit less and move more,” he added.  

The study was published online in JAMA Network Open.

The study involved 7,607 U.S. individuals without a history of stroke, with oversampling from the southeastern “Stroke Belt,” who were participating in the REGARDS cohort study.

The participants wore an accelerometer to measure physical activity and sedentary behavior for 7 consecutive days. The mean age of the individuals was 63 years; 54% were female, 32% were Black.

Over a mean follow-up of 7.4 years, 286 incident stroke cases occurred.

Results showed that increased levels of physical activity were associated with reduced risk of stroke.

For moderate to vigorous activity, compared with participants in the lowest tertile, those in the highest tertile of total daily time in moderate to vigorous activity had a 43% lower risk of stroke.

In the current study, the amount of moderate to vigorous activity associated with a significant reduction in stroke risk was approximately 25 minutes per day (3 hours per week).

Dr. Hooker noted that moderate to vigorous activity included things such as brisk walking, jogging, bike riding, swimming, or playing tennis or soccer. “Doing such activities for just 25 minutes per day reduced risk of stroke by 43%. This is very doable. Just commuting to work by bicycle would cover you here,” he said.

In terms of light-intensity activity, individuals who did 4-5 hours of light activities each day had a 26% reduced risk for first stroke, compared with those doing less than 3 hours of such light activities.

Dr. Hooker explained that examples of light activity included household chores, such as vacuuming, washing dishes, or going for a gentle stroll. “These activities do not require heaving breathing, increased heart rate or breaking into a sweat. They are activities of daily living and relatively easy to engage in.”

But he pointed out that the 4-5 hours of light activity every day linked to a reduction in stroke risk may be more difficult to achieve than the 25 minutes of moderate to vigorous activity, saying: “You have to have some intentionality here.”
 

Long bouts of sedentary time are harmful

The study also showed that sedentary time was associated with a higher risk for stroke.

The authors noted that time spent in sedentary behavior is of interest because most adults spend most of their awake time being physically inactive.

They report that participants in the highest tertile of sedentary time (more than 13 hours/day) exhibited a 44% increase in risk of stroke, compared with those in the lowest tertile (less than 11 hours/day), and the association remained significant when adjusted for several covariates, including moderate to vigorous activity.

“Even when controlling for the amount of other physical activity, sedentary behavior is still highly associated with risk of stroke. So even if you are active, long bouts of sedentary behavior are harmful,” Dr. Hooker commented.

They also found that longer bouts of sedentary time (more than 17 minutes at a time) were associated with a 54% higher risk of stroke than shorter bouts (less than 8 minutes).

“This suggests that breaking up periods of sedentary behavior into shorter bouts would be beneficial,” Dr. Hooker said.

“If you are going to spend the evening on the couch watching television, try to stand up and walk around every few minutes. Same for if you are sitting at a computer all day – try having a standing workstation, or at least take regular breaks to walk around,” he added.

This research was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Additional funding was provided by an unrestricted grant from the Coca-Cola Company. The authors report no disclosures.

A version of this article first appeared on Medscape.com.

Spending more time doing light-intensity activities and less time being sedentary was associated with a reduced risk for first stroke in a population-based study of middle aged and older adults.

The study also found relatively short periods of moderate to vigorous exercise were associated with reduced stroke risk.

“Our results suggest there are a number of ways to reduce stroke risk simply by moving about,” said lead author Steven P. Hooker, PhD, San Diego State University. “This could be with short periods of moderate to vigorous activity each day, longer periods of light activity, or just sedentary for shorter periods of time. All these things can make a difference.”

Dr. Hooker explained that, while it has been found previously that moderate to vigorous exercise reduces stroke risk, this study gives more information on light-intensity activities and sedentary behavior and the risk of stroke.

“Our results suggest that you don’t have to be a chronic exerciser to reduce stroke risk. Replacing sedentary time with light-intensity activity will be beneficial. Just go for a short walk, get up from your desk and move around the house at regular intervals. That can help to reduce stroke risk,” Dr. Hooker said.  

“Our message is basically to sit less and move more,” he added.  

The study was published online in JAMA Network Open.

The study involved 7,607 U.S. individuals without a history of stroke, with oversampling from the southeastern “Stroke Belt,” who were participating in the REGARDS cohort study.

The participants wore an accelerometer to measure physical activity and sedentary behavior for 7 consecutive days. The mean age of the individuals was 63 years; 54% were female, 32% were Black.

Over a mean follow-up of 7.4 years, 286 incident stroke cases occurred.

Results showed that increased levels of physical activity were associated with reduced risk of stroke.

For moderate to vigorous activity, compared with participants in the lowest tertile, those in the highest tertile of total daily time in moderate to vigorous activity had a 43% lower risk of stroke.

In the current study, the amount of moderate to vigorous activity associated with a significant reduction in stroke risk was approximately 25 minutes per day (3 hours per week).

Dr. Hooker noted that moderate to vigorous activity included things such as brisk walking, jogging, bike riding, swimming, or playing tennis or soccer. “Doing such activities for just 25 minutes per day reduced risk of stroke by 43%. This is very doable. Just commuting to work by bicycle would cover you here,” he said.

In terms of light-intensity activity, individuals who did 4-5 hours of light activities each day had a 26% reduced risk for first stroke, compared with those doing less than 3 hours of such light activities.

Dr. Hooker explained that examples of light activity included household chores, such as vacuuming, washing dishes, or going for a gentle stroll. “These activities do not require heaving breathing, increased heart rate or breaking into a sweat. They are activities of daily living and relatively easy to engage in.”

But he pointed out that the 4-5 hours of light activity every day linked to a reduction in stroke risk may be more difficult to achieve than the 25 minutes of moderate to vigorous activity, saying: “You have to have some intentionality here.”
 

Long bouts of sedentary time are harmful

The study also showed that sedentary time was associated with a higher risk for stroke.

The authors noted that time spent in sedentary behavior is of interest because most adults spend most of their awake time being physically inactive.

They report that participants in the highest tertile of sedentary time (more than 13 hours/day) exhibited a 44% increase in risk of stroke, compared with those in the lowest tertile (less than 11 hours/day), and the association remained significant when adjusted for several covariates, including moderate to vigorous activity.

“Even when controlling for the amount of other physical activity, sedentary behavior is still highly associated with risk of stroke. So even if you are active, long bouts of sedentary behavior are harmful,” Dr. Hooker commented.

They also found that longer bouts of sedentary time (more than 17 minutes at a time) were associated with a 54% higher risk of stroke than shorter bouts (less than 8 minutes).

“This suggests that breaking up periods of sedentary behavior into shorter bouts would be beneficial,” Dr. Hooker said.

“If you are going to spend the evening on the couch watching television, try to stand up and walk around every few minutes. Same for if you are sitting at a computer all day – try having a standing workstation, or at least take regular breaks to walk around,” he added.

This research was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Additional funding was provided by an unrestricted grant from the Coca-Cola Company. The authors report no disclosures.

A version of this article first appeared on Medscape.com.

Spending more time doing light-intensity activities and less time being sedentary was associated with a reduced risk for first stroke in a population-based study of middle aged and older adults.

The study also found relatively short periods of moderate to vigorous exercise were associated with reduced stroke risk.

“Our results suggest there are a number of ways to reduce stroke risk simply by moving about,” said lead author Steven P. Hooker, PhD, San Diego State University. “This could be with short periods of moderate to vigorous activity each day, longer periods of light activity, or just sedentary for shorter periods of time. All these things can make a difference.”

Dr. Hooker explained that, while it has been found previously that moderate to vigorous exercise reduces stroke risk, this study gives more information on light-intensity activities and sedentary behavior and the risk of stroke.

“Our results suggest that you don’t have to be a chronic exerciser to reduce stroke risk. Replacing sedentary time with light-intensity activity will be beneficial. Just go for a short walk, get up from your desk and move around the house at regular intervals. That can help to reduce stroke risk,” Dr. Hooker said.  

“Our message is basically to sit less and move more,” he added.  

The study was published online in JAMA Network Open.

The study involved 7,607 U.S. individuals without a history of stroke, with oversampling from the southeastern “Stroke Belt,” who were participating in the REGARDS cohort study.

The participants wore an accelerometer to measure physical activity and sedentary behavior for 7 consecutive days. The mean age of the individuals was 63 years; 54% were female, 32% were Black.

Over a mean follow-up of 7.4 years, 286 incident stroke cases occurred.

Results showed that increased levels of physical activity were associated with reduced risk of stroke.

For moderate to vigorous activity, compared with participants in the lowest tertile, those in the highest tertile of total daily time in moderate to vigorous activity had a 43% lower risk of stroke.

In the current study, the amount of moderate to vigorous activity associated with a significant reduction in stroke risk was approximately 25 minutes per day (3 hours per week).

Dr. Hooker noted that moderate to vigorous activity included things such as brisk walking, jogging, bike riding, swimming, or playing tennis or soccer. “Doing such activities for just 25 minutes per day reduced risk of stroke by 43%. This is very doable. Just commuting to work by bicycle would cover you here,” he said.

In terms of light-intensity activity, individuals who did 4-5 hours of light activities each day had a 26% reduced risk for first stroke, compared with those doing less than 3 hours of such light activities.

Dr. Hooker explained that examples of light activity included household chores, such as vacuuming, washing dishes, or going for a gentle stroll. “These activities do not require heaving breathing, increased heart rate or breaking into a sweat. They are activities of daily living and relatively easy to engage in.”

But he pointed out that the 4-5 hours of light activity every day linked to a reduction in stroke risk may be more difficult to achieve than the 25 minutes of moderate to vigorous activity, saying: “You have to have some intentionality here.”
 

Long bouts of sedentary time are harmful

The study also showed that sedentary time was associated with a higher risk for stroke.

The authors noted that time spent in sedentary behavior is of interest because most adults spend most of their awake time being physically inactive.

They report that participants in the highest tertile of sedentary time (more than 13 hours/day) exhibited a 44% increase in risk of stroke, compared with those in the lowest tertile (less than 11 hours/day), and the association remained significant when adjusted for several covariates, including moderate to vigorous activity.

“Even when controlling for the amount of other physical activity, sedentary behavior is still highly associated with risk of stroke. So even if you are active, long bouts of sedentary behavior are harmful,” Dr. Hooker commented.

They also found that longer bouts of sedentary time (more than 17 minutes at a time) were associated with a 54% higher risk of stroke than shorter bouts (less than 8 minutes).

“This suggests that breaking up periods of sedentary behavior into shorter bouts would be beneficial,” Dr. Hooker said.

“If you are going to spend the evening on the couch watching television, try to stand up and walk around every few minutes. Same for if you are sitting at a computer all day – try having a standing workstation, or at least take regular breaks to walk around,” he added.

This research was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Additional funding was provided by an unrestricted grant from the Coca-Cola Company. The authors report no disclosures.

A version of this article first appeared on Medscape.com.